Value-Based Care: In Multiple Myeloma

Value-BasedCare IN MulTIPlE MyEloMA

™

SEPTEMBER 2011

EDITORIAL ADVISORY BOARD Leon H. Dragon, MD, FACP Medical Director Kellogg Cancer Center Northshore University HealthSystem Clinical Assistant Professor of Medicine University of Chicago Pritzker School of Medicine

Charles M. Farber, MD, PhD Section Chief of Hematology and Oncology Department of Medicine Carol G. Simon Cancer Center

Jonathan L. Kaufman, MD Assistant Professor of Hematology and Oncology Winship Cancer Institute of Emory University

James T. Kenney Jr, RPh, MBA Pharmacy Operations Manager Harvard Pilgrim Health Care, Inc

Ira Klein, MD, MBA, FACP Medical Director Aetna Pharmacy Management

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4th IN A 6-PART SERIES

Side Effect Management in the Treatment of Multiple Myeloma Introduction The incorporation of novel therapies into the treatment paradigm for multiple myeloma (MM) has extended survival and improved the lives of patients. Individuals treated with newer therapies are surviving approximately 50% longer than similar patient populations treated with older regimens 10 years ago.1 The proteasome inhibitor bortezomib and the immunomodulators thalidomide and lenalidomide have demonstrated striking efficacy in clinical trials, and their inclusion in treatment regimens is now an evidence-based standard of care for the disease. The increased use of autologous stem cell transplant (ASCT) has also resulted in prolonged survival in myeloma patients.2,3 However, these dramatic improvements have come at a cost: the use of novel agents and ASCT

has substantially increased the economic burden associated with myeloma care. Two recent presentations described estimates of the overall costs associated with treatment.4,5 One study compared 18 regimens and found considerable variations in both the weekly cost of treatment ($766-$4940) and the overall response rate (ORR) (39%-92%).

The weekly cost per ORR ranged from $957 for treatment with a regimen of bortezomib, dexamethasone, and doxorubicin to $8821 for a regimen of bortezomib, melphalan, prednisone, and thalidomide.4 The other study compared the incremental cost-effectiveness over a 20-year lifetime horizon of 2 myeloma regimens: bortezomib, melphalan, and prednisone (VMP) and melphalan, prednisone, and lenalidomide plus continuous lenalidomide maintenance (MPR-R).5 For

Noopur S. Raje, MD Assistant Professor of Medicine Harvard Medical School Director, Center for Multiple Myeloma Massachusetts General Hospital

G. David Roodman, MD, PhD Professor, University of Pittsburgh School of Medicine Director, Bone Biology Center University of Pittsburgh Medical Center

Winston Wong, PharmD Associate Vice President Pharmacy Management CareFirst BlueCross BlueShield

EDITOR’S NOTE With the goal of promoting a better understanding of the relationship between cost and clinical outcomes, the Association for Value-Based Cancer Care® is publishing a newsletter series to address various aspects of value-based care for patients with multiple myeloma (MM). These publications report on the latest clinical updates pertaining to the management of the disease, and provide stakeholder perspectives on how these data can be used to promote high-quality, cost-effective care. Previous newsletters in this series (available at www.AVBCConline.org) discussed therapeutic choices based on the presence of high-risk cytogenetic abnormalities, the relevance of end points in clinical trials for MM, and the impact of novel agents on myeloma-associated renal impairment. In this fourth issue, we will focus on the value of incorporating best practices for managing treatment-related toxicities. Subsequent issues will address the potential economic implications of novel agents used to treat myeloma-related bone complications and value-based benefit design considerations for the disease.

S TA K E H O L D E R S ’ P E R S P E C T I V E S

This newsletter has been supported by funding from Millennium Pharmaceuticals, Inc.

Value-Based Approach to Managing Adverse Events in Myeloma.....................................................9 Atheer A. Kaddis, PharmD

Preventing and Treating Peripheral Neuropathy in Myeloma ...........................................................10 Stephanie S. Minich, PharmD, BCOP

An official publication of

this comparison, investigators used response and survival data from the phase 3 VISTA trial, which compared melphalan and prednisone (MP) with VMP, and the MM-015 trial, which compared MP with MPR-R. Costs included per-protocol drug and medical costs, treatment-related toxicities, second-line therapy, and resource utilization. In the VISTA trial, VMP provided a survival benefit over MP (hazard ratio [HR]=0.65), whereas in MM-015, MPR-R showed no survival benefit over MP (median follow-up, 21 months). Estimated overall survival (OS) was 4.187 years with VMP and 3.409 years with MPR-R over a lifetime horizon. Lifetime direct medical costs for these regimens were $119,102 and $241,247, respectively. In terms of OS, it was determined that MPR-R would become cost-effective only at an HR of £0.25 compared with MP.5 In addition to drug acquisition and provision of transplant services, other factors must be considered when assessing the costs associated with MM treatment. For example, novel agents have distinct toxicity profiles that may raise utilization costs related to provider services and medications required to treat adverse events (AEs). These toxicities may also have a negative effect on productivity and health-related quality of life (HRQOL). In addition, ASCT can lead to severe myelosuppression and other complications, thereby increasing the incidence and length of hospitalization and the need for ancillary services ranging from growth-factor support to psychobehavioral interventions. Given the proven efficacy of novel agents in the frontline setting, investigators are now questioning whether ASCT can be delayed in some cases until the time of relapse.6 This issue remains a subject of ongoing debate and will continue to be investigated in clinical trials.

Novel agents have distinct toxicity profiles that may raise utilization costs related to provider services and medications required to treat adverse events.

In today’s healthcare environment, it is important to analyze all aspects of disease management—including the cost of preventing and minimizing AEs—when making value-based decisions regarding care. Therefore, the safety profiles of bortezomib, thalidomide, and lenalidomide must be considered in any economic evaluation of myeloma treatment. This article discusses some of the major AEs associated with each of these novel agents, along with prevention and management strategies and related cost considerations.

Bortezomib In clinical trials evaluating bortezomib as monotherapy for the treatment of myeloma, major AEs that emerged were neurotoxicity and myelosuppression.7-12 When this agent was compared with high-dose dexamethasone in the relapsed setting, common grade 3 or 4 AEs reported in bortezomib-treat-

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ed patients were thrombocytopenia (30%), neutropenia (14%), and peripheral neuropathy (PN) (8%).10 In 2 studies of bortezomib plus dexamethasone in relapsed or refractory MM, the incidence and type of toxicities were similar to those seen in trials of bortezomib alone.7,13

In today’s healthcare environment, it is important to analyze all aspects of disease management when making value-based decisions regarding care.

In the VISTA trial of newly diagnosed, transplant-ineligible patients with MM,14 myelosuppression was similar in the 2 groups, but neurotoxicity was more common with VMP than with MP (44% vs 5%, respectively). However, the PN was reversible in 74% of patients; it resolved in 56% of patients and decreased by 1 or more grades in 18% of patients within a median of 2 months. Grade 3 or 4 gastrointestinal toxicities were also more common in the VMP group than in the MP group (19% vs 5%, respectively). Similarly, the incidence of any grade of herpes zoster was higher in patients receiving bortezomib than in those receiving MP alone (13% vs 4%, respectively), although viral prophylaxis was not required in this trial and many patients did not receive it.

Managing bortezomib-associated myelosuppression Bortezomib-associated thrombocytopenia and neutropenia follow a cyclical pattern. Platelet and neutrophil nadirs occur after the last dose of each treatment cycle; counts typically recover prior to the start of the next cycle. Platelet counts of patients receiving bortezomib twice weekly decrease during each 21-day cycle of treatment and reach a nadir of about 40% of baseline following the last dose of each cycle.15 No evidence of cumulative thrombocytopenia or neutropenia has been observed in clinical trials. Platelet and neutrophil counts should be monitored and dose-adjusted when needed to ameliorate the degree of myelosuppression; if necessary, a transfusion may be considered.15-17 Cost drivers for thrombocytopenia and neutropenia include nursing and pharmacy time needed for dose adjustments and patient counseling, and treatment modalities such as transfusions and growth-factor support. In cases of neutropenia-related infection, treatment with antimicrobial agents as well as office, emergency, and hospital visits must also be considered.18 Managing bortezomib-induced neuropathy In clinical trials of bortezomib in the relapsed MM setting, baseline neuropathy has been documented in some patients; this may be due to the prior use of neurotoxic agents such as vincristine, cisplatin, and thalidomide.19 Neuropathy may also be caused by the myeloma itself, and approximately 3% to 13% of patients present with this condition at the time of diagnosis, prior to the initiation of therapy.20 However, the

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inclusion of bortezomib may exacerbate Table 1. Recommended Bortezomib Dose Modifications15 the risk of this toxicity. In newly diagnosed MM patients initially treated with borSeverity of Peripheral Neuropathy Modification of Dose and Regimen tezomib in clinical trials, grades 1 and 2 neuropathy affected approximately 24% to No action Grade 1 (paresthesia or loss of reflex) 33% of patients, whereas grades 3 and 4 PN without pain or loss of function developed in up to 18% of patients.19,21 Reduce bortezomib dose from 1.3 Grade 1 with pain or grade 2 Age is a major risk factor for the develto 1.0 mg/m2 (interferes with function but not with opment of bortezomib-induced peripheral activities of daily living) neuropathy (BIPN); this risk increases Withhold bortezomib until toxicity Grade 2 with pain or grade 3 about 6% per year of advancing age.22 resolves, then reinitiate at a dose (interferes with activities of daily living) Other risk factors identified in clinical triof 0.7 mg/m2 once weekly als include therapy duration, dose intensity, cumulative dose, comorbid conditions Discontinue bortezomib Grade 4 (permanent sensory loss that (eg, diabetes mellitus, alcoholism), and the interferes with function) presence of preexisting neuropathy.23 A recent subanalysis of the VISTA trial, however, found that the only consistent risk factor for PN was Nonpharmacologic management of sensory PN and neurobaseline neuropathy.21 pathic pain may include the use of daily vitamins, nutritional Bortezomib appears to induce neurotoxicity via axonal desupplements, topical therapies, and physical manipulation. generation.24,25 This often occurs within the first cycle of Vitamins and supplements include certain B vitamins (B1, B6, treatment and does not seem to increase after the fifth cycle.26 B12), folic acid, magnesium, potassium, vitamin E, acetyl L-carIn the VISTA trial, the median time to onset of PN was 2.3 nitine, alpha-lipoic acid, and L-glutamine. Topical and physimonths.21 BIPN usually begins as a sensory phenomenon, cal interventions include emollient creams (eg, cocoa butter, with numbness or tingling in the upper and lower extremities, menthol, and eucalyptus-based creams), physical therapy, and or as a sensation of burning or cold.26 Sometimes, it progresstherapeutic massage.23,30 These recommendations are based es to neuropathic pain, with painful shooting or cramping on anecdotal evidence and have not been confirmed in clinsensations. Another neuropathic manifestation associated ical trials. Pharmacologic therapy for PN includes gabapentin, with bortezomib is autonomic dysfunction, resulting in pregabalin, nortriptyline, duloxetine, and topical lidocaine, hypotension and gastrointestinal toxicities, such as diarrhea, based on short-term studies in other indications such as post nausea, and constipation.23 herpetic neuralgia and painful diabetic neuropathy.23,30 The incidence of PN may be reduced by replacing conventional twice-weekly intravenous (IV) dosing with alternative dosing strategies. In a recent phase 3 trial, administering IV bortezomib once per week reduced the incidence of grade 3 or 4 PN to 8% (compared with 28% in patients receiving twiceweekly dosing). Efficacy was essentially the same for both groups.27 Administering bortezomib as a subcutaneous (SC) injection also appears to be effective for reducing the incidence of neuropathy without sacrificing therapeutic benefit.

In a recent clinical trial, SC dosing was shown to be noninfeAlthough it is certainly advantageous to have several oprior to IV dosing on efficacy end points.28 tions to manage BIPN, most interventions are associated with The neurotoxic effects of bortezomib are generally re additional expenses. Nursing and pharmacy time, costs for versible with dose reduction or treatment discontinuation. drugs and supplements to control neuropathic symptoms, and According to a subanalysis of the VISTA trial, 79% of neurofees for massages, physical therapy, and assistive devices all pathic events improved by at least 1 grade within a median of contribute to the economic burden. Moreover, neuropathic 1.9 months; 60% of events completely resolved within a symptoms can interfere with dressing, writing, keyboarding, median of 5.7 months.21 The dose of bortezomib should be ad household chores, ambulation, and many other activities of justed according to recommendations in the prescribing infordaily living that affect HRQOL and work productivity. Data mation, which are based on severity and degree of associated suggest that an event of therapy-related PN induced by any neuropathic pain or impaired function (Table 1).15 The benchemotherapy drug (bortezomib included) costs approximateefits of dose modification have been shown in a phase 3 trial ly $4900 in lost productivity and at-home care.31 of single-agent bortezomib, with resolution or improvement of grade 2 or higher PN observed in 68% of patients who Managing bortezomib-associated varicella zoster virus underwent a prespecified dose-reduction protocol, compared Treatment with bortezomib is also associated with reactivawith 47% of those who did not.29 tion of varicella zoster virus (VZV). An analysis of data from

Administering bortezomib as a subcutaneous injection also appears to be effective for reducing the incidence of neuropathy without sacrificing therapeutic benefit.

Value-Based Care in Multiple Myeloma

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Figure. Incidence of all AEs and DVT in the ECOG E4A03 trial of RD versus Rd.42 60

RD 50

Rd

were significantly reduced in the ECOG E4A03 study of newly diagnosed MM patients that compared a standard regimen of lenalidomide plus high-dose dexamethasone with lenalidomide plus low-dose dexamethasone.42 Thromboprophylaxis was recommended but not mandated until late in the study. Grade 3 or 4 deep vein thrombosis (DVT) occurred in 12% of patients treated with low-dose dexamethasone compared with 26% of patients assigned to high-dose dexamethasone (Figure).

Patients (%)

40

30

20

10

0

All AEs

DVT

All between-group differences were statistically significant (P£.04).

AEs indicates adverse events; DVT, deep vein thrombosis; ECOG, Eastern Cooperative Oncology Group; Rd, lenalidomide plus low-dose dexamethasone; RD, lenalidomide plus high-dose dexamethasone.

a phase 3 clinical trial of relapsed/refractory MM demonstrated that bortezomib treatment resulted in a significantly increased incidence of VZV reactivation compared with highdose dexamethasone (13% vs 5%, respectively).32 Most VZV infections were grade 1 or 2, and the incidence of grade 3 or 4 infections was similar in bortezomib- and dexamethasonetreated patients (1.8% vs 1.5%, respectively). Patients receiving bortezomib should be monitored for virus reactivation, and should be prescribed acyclovir as prophylaxis.33 Acyclovir is available as a relatively inexpensive generic formulation,34 enhancing the value of prophylaxis. Antiviral prophylaxis is also valuable because it prevents the costs and diminished HRQOL associated with a painful herpes zoster infection and postherpetic neuralgia.

Lenalidomide Two major AEs associated with lenalidomide use in pa tients with relapsed or refractory MM are myelosuppression and venous thromboembolism (VTE). Pooled data from 2 studies comparing lenalidomide plus dexamethasone with dexamethasone alone reported the following rates of grade 3 or 4 AEs: neutropenia (35%), anemia (11%), thrombocytopenia (13%), infection (16%), and VTE (13%).35,36 Similar toxicity profiles have been reported in other studies of lenalidomide-based combination regimens.37-40 In patients treated with lenalidomide plus dexamethasone, grade 3 or 4 VTE ranged from 3% to 26%, depending on whether they received thromboprophylaxis.41 Toxicities (with the exception of grade 3 or 4 neutropenia)

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Managing lenalidomide-associated VTE Aspirin, warfarin, and low-molecular-weight heparin (LMWH) have all been used for routine thromboprophylaxis in lenalidomide-treated patients, but it has not been determined whether this approach reduces the incidence of thromboembolic events.43 The decision to use thromboprophylaxis must be based on the anticipated risk of thrombosis in the individual patient. Prophylactic agents should be used only when necessary, since they present additional serious risks, notably bleeding and hemorrhagic stroke.44 For example, because lenalidomide alone does not induce a high risk of VTE, thromboprophylaxis is not recommended when lenalidomide is used as monotherapy.45 Cost of prophylaxis is not prohibitive, but the expense associated with treatment of DVT and pulmonary embolism increases the overall cost of lenalidomide-based therapy.

Hospitalization and treatment for an index episode of DVT has been estimated at greater than $20,000 in 2002 dollars.46 If VTE does occur, rapid intervention may help reduce complications that increase the cost of care. Therefore, patients and caregivers should be educated on the signs of this toxicity and instructed to seek treatment promptly if symptoms arise.

The expense associated with treatment of DVT and pulmonary embolism increases the overall cost of lenalidomide-based therapy.

Managing lenalidomide-associated myelosuppression Myelosuppression is a serious AE associated with lenalidomide.44,47 When platelet counts fall to <30,000/mcL, lenalidomide treatment should be halted. Treatment may be resumed when platelet counts return to ≥30,000/mcL at a dose reduced from the standard 25 mg/day to 15 mg/day.44 When neutrophil counts fall to <1000/mcL, lenalidomide treatment should be halted and granulocyte colony-stimulating factor (G-CSF) should be added. Lenalidomide treatment may continue at 25 mg/day when neutrophil counts return to ≥1000/mcL, provided neutropenia is the only toxicity; lenalidomide should be restarted at 15 mg/day on return to ≥1000/mcL in the presence of any additional toxicity. For each subsequent drop in the neutrophil count <1000/mcL, lenalidomide should be interrupted and resumed when the

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count returns to â&#x2030;Ľ1000/mcL, using a dose of 5 mg less than the previous dose to a minimum of 5 mg/day total dose.44 Anemia can be managed with erythropoiesis-stimulating agents (ESAs), which are only recommended when hemoglobin levels fall to <9 g/dL, especially in patients with cardiac disease. For patients without cardiac disease, ESAs may increase the risk of VTE and should be used with caution. The use of these agents (as well as G-CSFs) may add substantially to the cost of lenalidomide treatment.

Table 2. Recommended Thalidomide Dose Modifications61 Severity of Peripheral Neuropathy

Modification of Dose and Regimen

Grade 1 (mild)

No action

Grade 1 with pain or grade 2

Intermittent symptoms: Continue therapy Continuous symptoms: Withhold thalidomide until toxicity resolves, then reduce dose

Grade 3

Withhold thalidomide until toxicity resolves then restart at reduced dose

Grade 4 (permanent sensory loss that

Discontinue thalidomide

Thalidomide interferes with function) Major grade 3 or 4 AEs associated with thalidomide use include constipation, neuropathy, somnolence, depression, and VTE. A trial evaluating should be reinitiated only if the neuropathy returns to basesingle-agent thalidomide in relapsed or refractory MM reportline status. TIPN may be reversible in some cases, but symped that most AEs were mild or moderate and dose dependtoms tend to resolve slowly; this agent is known to cause perent.48 At a dose of 200 mg, approximately 25% of patients had manent nerve damage and irreversible neuropathy in some no appreciable toxicities, but at higher doses virtually all cases.61-63 When neuropathy is sustained, economic burden patients experienced grade 1 or 2 toxicities. Less than 5% of can be high; productivity and activities of daily living are patients reported grade 1 or 2 leukopenia at any dose.48 A sysaffected permanently; and there may be a need for ongoing tematic review of clinical trials of single-agent thalidomide pharmacologic and nonpharmacologic interventions. showed that the most frequent grade 3 or 4 AEs were constipation (16%), somnolence (11%), neuropathy (6%), rash (3%), VTE (3%), and cardiac toxicity (2%).49 When thalidomide is combined with other agents, the incidence of AEs tends to increase. In a recent review of 12 trials of thalidomide plus dexamethasone (TD) in patients with relapsed or refractory MM, the major AEs were constipation (37%), neuropathy (27%), somnolence (26%), depression (10%), and VTE (5%).50 Among patients with newly diagnosed MM, combining thalidomide with other agents appears to increase Managing thalidomide-associated VTE severe toxicities associated with thalidomide, including conVTE is a serious toxicity observed in MM patients treated stipation, neuropathy, somnolence, and VTE. These combiwith thalidomide in combination with anthracyclines and nations include: TD51-53; thalidomide, cyclophosphamide, and dexamethasone.64 In a trial of newly diagnosed patients who 54 dexamethasone ; thalidomide, doxorubicin, dexamethasone, received induction chemotherapy plus dexamethasone with and melphalan55; thalidomide, melphalan, and prednisone56or without thalidomide, DVT developed in 28% of patients 59 ; and thalidomide, vincristine, liposomal doxorubicin, and who received thalidomide, compared with just 4% of patients dexamethasone.60 who did not.65 All DVT episodes occurred within the first 3 induction cycles, and thalidomide was safely resumed in 75% Managing thalidomide-induced neuropathy of patients receiving anticoagulation therapy.

Thalidomide-induced peripheral neuropathy (TIPN) is a Low-dose aspirin, warfarin, and LMWH are currently reccommon and potentially serious AE.61 Half of all patients ommended as thromboprophylaxis for patients receiving treated with thalidomide experience distal sensory PN even thalidomide.45,66-69 All 3 agents can be effective, but more rewith low doses (25-50 mg); in some studies up to 80% of search is needed to determine which prophylactic strategy patients developed neuropathy, with the frequency of grade 3 will consistently reduce the risk of VTE to a goal of <10% of or 4 events ranging from 3% to >15%.47 TIPN is cumulative patients.45 An expert panel has recommended LMWH and dose dependent, and is therefore managed with dose re(equivalent to enoxaparin 40 mg/day) or full-dose warfarin duction or discontinuation (Table 2).61 Patients should be (international normalized ratio 2-3) for thalidomide- and monitored for early signs of neuropathy, particularly during lenalidomide-treated patients with â&#x2030;Ľ2 individual or myelothe first 3 months of treatment.61 If symptoms develop, ma-related risk factors, and for all patients receiving concurthalidomide should be discontinued immediately to limit furrent high-dose dexamethasone, doxorubicin, or multiagent ther damage, if clinically appropriate.61 Usually, thalidomide chemotherapy (Table 3).45 There are incremental cost differ-

Low-dose aspirin, warfarin, and LMWH are currently recommended as thromboprophylaxis for patients receiving thalidomide.

Value-Based Care in Multiple Myeloma

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Table 3. Risk Assessment for VTE Prophylaxis in Patients Treated with Immunomodulatory Agents45 Individual Risk Factors

Treatment-Related Risk Factors 2

Obesity (BMI ≥30 kg/m ) Previous venous thromboembolism

High-dose dexamethasone (≥480 mg/month or 120 mg/week)

Central venous catheter or pacemaker

Doxorubicin

Chronic renal disease (CrCl <40 mL/min)

Combination chemotherapy

Diabetes Medications (erythropoietin, estrogen) Immobility General surgery Trauma (major or lower extremity) Blood clotting disorders Number of Risk Factors

Prophylaxis

0-1

Aspirin 81-325 mg daily

2+

LMWH (enoxaparin 40 mg SC daily, or equivalent)

Conclusion Over the past decade, advances in MM therapy have improved outcomes as well as increased the cost of care. In addition to acquisition and service charges for antimyeloma treatment, other key cost drivers exist, including the impact of treatment-related toxicities on utilization, patient productivity, and HRQOL. The potential costs associated with serious AEs such as PN, infection due to myelosuppression, and VTE must be factored into any balanced economic assessment of myeloma care.46 Value-based treatment requires careful analysis of the total economic burden levied by each treatment option, including all contributors to direct and indirect costs. Such an analysis may reveal that the cost of a drug or service is justified by better overall outcomes as well as savings that accrue when AEs are prevented and managed effectively. ■ References

1. Kumar SK, Rajkumar SV, Dispenzieri A, et al. ImWarfarin (INR 2-3) proved survival in multiple myeloma and the impact of novel therapies. Blood. 2008;111:2516-2520.

2. Gore ME, Selby PJ, Viner C, et al. Intensive treatBMI indicates body mass index; CrCl, creatinine clearance; INR, international normalized ratio; ment of multiple myeloma and criteria for complete reLMWH, low-molecular-weight heparin; SC, subcutaneously; VTE, venous thromboembolism. mission. Lancet. 1989;334:879-882.

3. Anderson KC, Barut BA, Ritz J, et al. Autologous bone marrow transplantation therapy for multiple myeloma. Eur J Haematol Suppl. 1989;51:157-163. ences between LMWH and the older anticoagulant warfarin 4. Blank PR, Levin R, Pestalozzi BC, et al. Cost differences among treatthat need to be considered. Pharmacoeconomic comparisons ment options for patients with refractory myeloma previously treated of LMWH and warfarin for prophylaxis in a noncancer setwith high-dose chemotherapy and autologous stem-cell transplantation: an analysis from the U.S. and Swiss perspectives. J Clin Oncol. ting suggest that outcomes, administration costs, and the need 2011;29(suppl). Abstract e16569. for frequent laboratory monitoring of warfarin are factors that 5. Wang S-T, Huang H, Ba-Mancini A, et al. The cost-effectiveness of should be analyzed in addition to drug price in determining bortezomib plus melphalan and prednisone versus lenalidomide plus melphalan and prednisone with continuous lenalidomide maintenance relative cost of care.70 Aspirin, an inexpensive over-thetreatment for the initial treatment of multiple myeloma in the United counter agent, can be used as prophylaxis for the subset of States. Blood (ASH Annual Meeting Abstracts). 2010;116. Abstract 2563. thalidomide-treated patients with £1 risk factor for VTE.45 6. Bensinger WI. Role of autologous and allogeneic stem cell transplantation in myeloma. Leukemia. 2009;23:442-448.

7. Jagannath S, Barlogie B, Berenson J, et al. A phase 2 study of two doses Managing thalidomide-associated neutropenia of bortezomib in relapsed or refractory myeloma. Br J Haematol. 2004; The use of thalidomide is associated with mild neutropenia 127:165-172.

8. Jagannath S, Barlogie B, Berenson JR, et al. Updated survival analyses in 3% to 15% of patients. This rate increases when thalidomide after prolonged follow-up of the phase 2, multicenter CREST study of is combined with other drugs, particularly myelotoxic agents.16 bortezomib in relapsed or refractory multiple myeloma. Br J Haematol.

Given the risk of infection, patients receiving thalidomide 2008;143:537-540.

9. Jagannath S, Durie BG, Wolf J, et al. Bortezomib therapy alone and in should be closely monitored with repeat differential and whole combination with dexamethasone for previously untreated symptoblood counts. If absolute neutrophil count (ANC) falls to matic multiple myeloma. Br J Haematol. 2005;129:776-783. <750/mcL, thalidomide should be re-evaluated and, if the neu10. Richardson PG, Sonneveld P, Schuster MW, et al. Bortezomib or highdose dexamethasone for relapsed multiple myeloma. N Engl J Med. tropenia persists, consideration should be given to withholding 2005;352:2487-2498.

61 treatment with this agent if clinically appropriate. The addi11. Richardson PG, Sonneveld P, Schuster MW, et al. Safety and efficacy tion of growth-factor support or a 50% dose reduction should of bortezomib in high-risk and elderly patients with relapsed multiple myeloma. Br J Haematol. 2007;137:429-435. be considered for those with an ANC of 500/mcL to 1000/mcL; 12. Richardson PG, Sonneveld P, Schuster M, et al. Extended follow-up of therapy should be discontinued immediately when this falls to a phase 3 trial in relapsed multiple myeloma: final time-to-event results <500/mcL.71 Thalidomide may be restarted at a 50% lower dose of the APEX trial. Blood. 2007;110:3557-3560.

13. Jagannath S, Richardson PG, Barlogie B, et al. Bortezomib in combinawith or without growth-factor support once neutropenia re tion with dexamethasone for the treatment of patients with relapsed solves.71 Other hematologic complications, including anemia, and/or refractory multiple myeloma with less than optimal response to leukopenia, and thrombocytopenia, are rarely associated with bortezomib alone. Haematologica. 2006;91:929-934. this agent.71,72 14. San Miguel JF, Schlag R, Khuageva NK, et al. Bortezomib plus melpha-

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lan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008;359:906-917.

15. Velcade [package insert]. Cambridge, MA: Millennium Pharmaceuticals; December 2009.

16. Gay F, Palumbo A. Multiple myeloma: management of adverse events.

Med Oncol. 2010;27:646-653.

17. Menashe J. Managing and avoiding bortezomib toxicity. Community Oncology. 2007;8:480-484.

18. Weycker D, Malin J, Edelsberg J, et al. Cost of neutropenic complications of chemotherapy. Ann Oncol. 2008;19:454-460.

19. Badros A, Goloubeva O, Dalal JS, et al. Neurotoxicity of bortezomib therapy in multiple myeloma: a single-center experience and review of the literature. Cancer. 2007;110:1042-1049.

20. Richardson PG, Xie W, Mitsiades C, et al. Single-agent bortezomib in previously untreated multiple myeloma: efficacy, characterization of peripheral neuropathy, and molecular correlations with response and neuropathy. J Clin Oncol. 2009;27:3518-3525.

21. Dimopoulos MA, Mateos MV, Richardson PG, et al. Risk factors for, and reversibility of, peripheral neuropathy associated with bortezomibmelphalan-prednisone in newly diagnosed patients with multiple myeloma: subanalysis of the phase 3 VISTA study. Eur J Haematol.

2011;86:23-31.

22. Corso A, Mangiacavalli S, Varettoni M, et al. Bortezomib-induced peripheral neuropathy in multiple myeloma: a comparison between previously treated and untreated patients. Leuk Res. 2010;34:471-474.

23. Richardson PG, Laubach JP, Schlossman RL, et al. Complications of multiple myeloma therapy, part 1: risk reduction and management of peripheral neuropathy and asthenia. J Natl Compr Cancer Netw. 2010; 8(suppl 1):S4-S12.

24. Cata JP, Weng HR, Burton AW, et al. Quantitative sensory findings in patients with bortezomib-induced pain. J Pain. 2007;8:296-306.

25. Cavaletti G, Gilardini A, Canta A, et al. Bortezomib-induced peripheral neurotoxicity: a neurophysiological and pathological study in the rat. Exp Neurol. 2007;204:317-325.

26. Richardson PG, Briemberg H, Jagannath S, et al. Frequency, characteristics, and reversibility of peripheral neuropathy during treatment of advanced multiple myeloma with bortezomib. J Clin Oncol. 2006;24: 3113-3120.

27. Bringhen S, Larocca A, Rossi D, et al. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood. 2010;116:4745-4753.

28. Moreau P, Pylypenko H, Grosicki S, et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol.

2011;12:431-440.

29. Richardson PG, Sonneveld P, Schuster MW, et al. Reversibility of symptomatic peripheral neuropathy with bortezomib in the phase III APEX trial in relapsed multiple myeloma: impact of a dose-modification guideline. Br J Haematol. 2009;144:895-903.

30. Delforge M, Bladé J, Dimopoulos MA, et al. Treatment-related peripheral neuropathy in multiple myeloma: the challenge continues. Lancet Oncol. 2010;11:1086-1095.

31. Hausheer FH, Schilsky RL, Bain S, et al. Diagnosis, management, and evaluation of chemotherapy-induced peripheral neuropathy. Semin Oncol. 2006;33:15-49.

32. Chanan-Khan A, Sonneveld P, Schuster MW, et al. Analysis of herpes zoster events among bortezomib-treated patients in the phase III APEX study. J Clin Oncol. 2008;26:4784-4790.

33. Vickrey E, Allen S, Mehta J, et al. Acyclovir to prevent reactivation of varicella zoster virus (herpes zoster) in multiple myeloma patients receiving bortezomib therapy. Cancer. 2009;115:229-232.

34. Johns Hopkins ABX Guide. www.hopkinsguides.com/hopkins/ub/view/ Johns_Hopkins_ABX_Guide/540007/all/Acyclovir. Accessed August 18, 2011.

35. Dimopoulos M, Spencer A, Attal M, et al. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007;357:2123-2132.

36. Weber DM, Chen C, Niesvizky R, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007;357:2133-2142.

37. Chen C, Reece DE, Siegel D, et al. Expanded safety experience with lenalidomide plus dexamethasone in relapsed or refractory multiple myeloma. Br J Haematol. 2009;146:164-170.

38. Morgan GJ, Schey SA, Wu P, et al. Lenalidomide (Revlimid), in combination with cyclophosphamide and dexamethasone (RCD), is an

effective and tolerated regimen for myeloma patients. Br J Haematol.

2007;137:268-269.

39. Baz R, Walker E, Karam MA, et al. Lenalidomide and pegylated liposomal doxorubicin-based chemotherapy for relapsed or refractory multiple myeloma: safety and efficacy. Ann Oncol. 2006;17:1766-1771.

40. Knop S, Gerecke C, Liebisch P, et al. Lenalidomide, adriamycin, and dexamethasone (RAD) in patients with relapsed and refractory multiple myeloma: a report from the German Myeloma Study Group DSMM (Deutsche Studiengruppe Multiples Myelom). Blood. 2009;113:4137-4143.

41. Mateos MV. Management of treatment-related adverse events in patients with multiple myeloma. Cancer Treat Rev. 2010;36(suppl 2):S24-S32.

42. Rajkumar SV, Jacobus S, Callander NS, et al. Lenalidomide plus highdose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol. 2010;11:29-37.

43. Hirsh J. Risk of thrombosis with lenalidomide and its prevention with aspirin. Chest. 2007;131:275-277.

44. Revlimid [package insert]. Summit, NJ: Celgene Corporation; October 2010.

45. Palumbo A, Rajkumar SV, Dimopoulos MA, et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma.

Leukemia. 2008;22:414-423.

46. Cook R. Economic and clinical impact of multiple myeloma to managed care. J Manag Care Pharm. 2008;14(7 suppl):19-25.

47. Schiff D, Wen PY, van den Bent MJ. Neurological adverse effects caused by cytotoxic and targeted therapies. Nat Rev Clin Oncol. 2009;6:596-603.

48. Singhal S, Mehta J, Desikan R, et al. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med. 1999;341:1565-1571.

49. Glasmacher A, Hahn C, Hoffmann F, et al. A systematic review of phase-II trials of thalidomide monotherapy in patients with relapsed or refractory multiple myeloma. Br J Haematol. 2006;132:584-593.

50. von Lilienfeld-Toal M, Hahn-Ast C, Furkert K, et al. A systematic review of phase II trials of thalidomide/dexamethasone combination therapy in patients with relapsed or refractory multiple myeloma. Eur J Haematol. 2008;81:247-252.

51. Rajkumar SV, Blood E, Vesole D, et al; Eastern Cooperative Oncology Group. Phase III clinical trial of thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: a clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol. 2006;24:431-436.

52. Ludwig H, Hajek R, Tóthová E, et al. Thalidomide-dexamethasone compared with melphalan-prednisolone in elderly patients with multiple myeloma. Blood. 2009;113:3435-3442.

53. Rajkumar SV, Rosiñol L, Hussein M, et al. Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol. 2008;26:2171-2177.

54. Morgan GJ, Davies FE, Gregory WM, et al. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation.

Blood. 2011;118:1231-1238.

55. Lokhorst HM, van der Holt B, Zweegman S, et al. A randomized phase 3 study on the effect of thalidomide combined with adriamycin, dexamethasone, and high-dose melphalan, followed by thalidomide maintenance in patients with multiple myeloma. Blood. 2010;115:1113-1120.

56. Palumbo A, Bringhen S, Caravita T, et al. Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial. Lancet. 2006;367:825-831.

57. Palumbo A, Bringhen S, Liberati AM, et al. Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood. 2008;112:3107-3114.

58. Hulin C, Facon T, Rodon P, et al. Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial. J Clin Oncol. 2009;27:3664-3670.

59. Facon T, Mary JY, Hulin C, et al. Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial. Lancet. 2007;370:1209-1218.

60. Zervas K, Dimopoulos MA, Hatzicharissi E, et al. Primary treatment of multiple myeloma with thalidomide, vincristine, liposomal doxorubicin and dexamethasone (T-VAD doxil): a phase II multicenter study. Ann Oncol. 2004;15:134-138.

61. Thalomid [package insert]. Summit, NJ: Celgene Corporation; February 2007.

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62. Wulff CH, Høyer H, Asboe-Hansen G, et al. Development of polyneuropathy during thalidomide therapy. Eur J Haematol. 2008;81:247-252.

63. Tseng S, Pak G, Washenik K, et al. Rediscovering thalidomide: a review of its mechanism of action, side effects, and potential uses. J Am Acad Dermatol. 1996;35:969-979.

64. van Marion AM, Auwerda JJ, Lisman T, et al. Prospective evaluation of coagulopathy in multiple myeloma patients before, during and after various chemotherapeutic regimens. Leuk Res. 2008;32:1078-1084.

65. Zangari M, Anaissie E, Barlogie B, et al. Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy. Blood. 2001;98:1614-1615.

66. Minnema MC, Breitkreutz I, Auwerda JJ, et al. Prevention of venous thromboembolism with low molecular-weight heparin in patients with multiple myeloma treated with thalidomide and chemotherapy.

Leukemia. 2004;18:2044-2046.

67. Zangari M, Barlogie B, Anaissie E, et al. Deep vein thrombosis in patients with multiple myeloma treated with thalidomide and chemo-

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therapy: effects of prophylactic and therapeutic anticoagulation. Br J Haematol. 2004;126:715-721.

68. Baz R, Li L, Kottke-Marchant K, et al. The role of aspirin in the prevention of thrombotic complications of thalidomide and anthracyclinebased chemotherapy for multiple myeloma. Mayo Clin Proc. 2005; 80:1568-1574.

69. Niesvizky R, Martínez-Baños D, Jalbrzikowski J, et al. Prophylactic lowdose aspirin is effective antithrombotic therapy for combination treatments of thalidomide or lenalidomide in myeloma. Leuk Lymphoma.

2007;48:2330-2337.

70. Dunn CJ, Goa KL. Enoxaparin. A pharmacoeconomic appraisal of its use in thromboembolic prophylaxis after total hip arthroplasty.

Pharmacoeconomics. 1996;10:179-190.

71. Ghobrial IM, Rajkumar SV. Management of thalidomide toxicity.

J Support Oncol. 2003;1:194-205.

72. Palumbo A, Facon T, Sonneveld P, et al. Thalidomide for treatment of multiple myeloma: 10 years later. Blood. 2008;111:3968-3977.

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PAYER PERSPECTIVE

Value-Based Approach to Managing Adverse Events in Myeloma

By Atheer A. Kaddis, PharmD Vice President, Managed Markets Diplomat Specialty Pharmacy, Flint, MI

O

ver the past decade, the use of bortezomib, lenalidomide, and thalidomide, with or without autologous stem cell transplant, has significantly improved outcomes for patients with multiple myeloma (MM). Several of the regimens now listed as category 1 recommendations by the National Comprehensive Cancer Network (NCCN) for the treatment of MM include 1 or more of these agents.1 Category 1 designation refers to uniform NCCN consensus that the intervention is appropriate based on high-level evidence. Individuals treated with new, more effective regimens are now surviving twice as long as those treated only a decade ago with therapies such as melphalan plus prednisone.2 These advances are truly revolutionary, as it is rare to see the emergence of therapies that can cause such a paradigm shift in the natural course of an incurable disease like MM. However, this excitement comes at a hefty price; namely, the direct and indirect costs associated with treatment. As a side note, this dilemma is not relegated exclusively to myeloma. We are now seeing new oncology therapies enter the market with a minimum of $100,000 per course of therapy, as evidenced by the targeted agents ipilimumab, for the treatment of melanoma, and brentuximab, for the treatment of lymphoma.3,4 This rise in the cost of therapy is not surprising; it was inevitable, as we have witnessed in the treatment of other disease states such as multiple sclerosis.5 The main article in this publication provides an excellent overview of side effects associated with bortezomib, lenalidomide, and thalidomide. I think it is important for clinicians and payers to focus considerable attention on the prevention and management of myelosuppression and venous thromboembolism (VTE), as they represent 2 ends of the spectrum as it relates to overall costs associated with care.

Myelosuppression as a complication of myeloma therapy cannot be overlooked. Granulocyte colony-stimulating factors are often required to manage this adverse event, and their use can significantly increase the overall cost of treatment. The addition of erythropoiesis-stimulating agents to lenalidomide-based therapy may also contribute greatly to the cost of care. It is important for clinicians and payers to be aware of the recommended guidelines pertaining to the

use of these products to prevent variability in utilization, which will inevitably result in additional costs that may not have been considered previously.6 Thromboembolism, on the other hand, is readily preventable with low-cost therapy. The cost of thromboprophylaxis with agents such as aspirin, warfarin, or low-molecular-weight heparin is very reasonable when compared with the high cost of treating deep vein thrombosis or pulmonary embolism once they occur. In addition, the incidence of VTE can often be reduced with lower doses of dexamethasone.7 In addition to side effect management, a key ingredient in providing value-based care for patients diagnosed with cancer is that of palliative care. This approach is aimed at improving the quality of life of patients and their families through prevention and relief of suffering by means of early identification, impeccable assessment, and tolerable treatment.8 For many patients diagnosed with cancer, the primary focus is on the various therapeutic options and the management of associated toxicities, while a discussion and plan involving palliative care is often overlooked. Palliative measures are most effective when implemented early in the course of treatment, and should be considered for every patient. Formulating a palliative care plan, in addition to being aware of the potential side effects of therapy and providing appropriate preventive and management strategies, are all critical to the overall success of treating MM. â&#x2013; References 1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Multiple Myeloma. Version 1.2011, NCCN Web site. www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. Accessed August 2011.

2. Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood.2008;111:2516-2520.

3. Murray L, ed. 2011 Red Book (Micromedex 2.0 Online). Montvale, NJ: Thompson PDR; 2011. Accessed May 25, 2011.

4. Seattle Genetics Sets Adcetris Price. BioCentury via BioPortfolio. www. bioportfolio.com/news/article/777951/Seattle-Genetics-Sets-AdcetrisPrice.html. Accessed August 27, 2011.

5. von Schaper E, Kresge N. Novartisâ&#x20AC;&#x2122; Gilenya spurs rivals to increase price.

Bloomberg News. http://articles.sfgate.com/2011-03-23/business/29176786_ 1_tysabri-avonex-novartis-spokesman/2. Accessed August 26, 2011.

6. Wright JD, Neugut AI, Wilde ET, et al. Physician characteristics and variability of erythropoiesis-stimulating agent use among Medicare patients with cancer. J Clin Oncol. 2011;29(suppl). Abstract 6020.

7. Rajkumar SV, Jacobus S, Callander NS, et al. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol. 2010;11:29-37.

8. World Health Organization. WHO Definition of Palliative Care. www. who.int/cancer/palliative/definition/en/. Accessed August 23, 2011.

Value-Based Care in Multiple Myeloma

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PHARMACIST PERSPECTIVE

Preventing and Treating Peripheral Neuropathy in Myeloma

By Stephanie S. Minich, PharmD, BCOP Clinical Pharmacist, Hematology/Oncology Clinical Assistant Professor University of Michigan Health System, Ann Arbor, MI

P

eripheral neuropathy (PN) is a potentially debilitating condition that can lead to significantly decreased quality of life and the interruption of vital therapy. In patients with multiple myeloma (MM), neuropathy may be a complication of the disease itself, or it may be a side effect of specific therapies.1,2 Bortezomib and thalidomide—2 very active agents in myeloma—have both been associated with the development of PN.2 Therefore, to ensure that patients remain on therapy, it is extremely important to prevent and/or minimize this painful symptom whenever possible.

Bortezomib-associated PN is well documented in MM but is generally reversible upon dose reduction or discontinuation.2,3 Recent studies evaluating a new administration route and dosing schedule of this agent have shown a reduced incidence of neuropathy, resulting in increased tolerability and decreased overall healthcare costs.

In a multicenter, randomized, phase 3 trial, Moreau and colleagues compared the efficacy and safety of subcutaneous (SC) versus intravenous (IV) bortezomib at the standard 1.3mg/m2 dose twice weekly in patients with previously treated MM.4 The overall response rates were similar in both groups of patients (42%). However, those in the SC group experienced significantly less overall PN than those in the IV group (38% vs 53%; P=.04).4 In addition, SC bortezomib does not appear to cause the hypotension that is sometimes associated with IV administration; therefore, fluid boluses may not be necessary when using the drug in this fashion. Thus, SC administration may result in decreased monitoring time in the infusion area and potentially less admissions for infusionrelated reactions. Indeed, an exciting opportunity may even exist for the administration of SC bortezomib at home, which would eliminate numerous infusion visits. It remains to be seen if this option is feasible, but the safety profile of SC bortezomib suggests that it is a possibility.

Administering bortezomib once weekly instead of twice weekly has also been shown to be of value in reducing the incidence of PN. In the phase 3 GIMEMA trial, Bringhen and colleagues compared once-weekly versus twice-weekly

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bortezomib in transplant-ineligible MM patients and found similar efficacy between groups, but with significantly decreased rates of grade 3/4 PN in the once-weekly group (8% vs 28%; P <.001).5 Therefore, it appears that administering bortezomib once weekly, in select patient populations, can produce good responses while allowing for fewer clinic visits (and thus decreased costs) and a lower incidence of treatment-related toxicity.

Thalidomide-associated PN is a cumulative and doserelated toxicity in MM.2,6 Unfortunately, the neuropathy caused by this agent may be irreversible if not identified early and managed appropriately. Therefore, it is imperative to assess patients regularly for the development of thalidomideassociated neuropathy and to promptly decrease and/or discontinue treatment when necessary, as discussed in the main article of this publication.7,8 Pharmacists play a vital role in helping patients to receive the greatest benefits from treatment. Assessing patients at every visit for signs and symptoms of PN is critical, as this allows for prompt dose modifications of bortezomib and thalidomide when necessary. Minimizing PN through the use of SC and once-weekly bortezomib offers a value-based approach to therapy. Strategies such as these can lead to increased dose intensity overall and improved response to therapy, thus optimizing care for the patient with myeloma. ■ References 1. Malhotra P, Choudhary PP, Lal V, et al. Prevalence of peripheral neuropathy in multiple myeloma at initial diagnosis. Leuk Lymphoma. 2011 Jul 13. [Epub ahead of print].

2. Delforge M, Bladé J, Dimopoulos MA, et al. Treatment-related peripheral neuropathy in multiple myeloma: the challenge continues. Lancet Oncol. 2010;11:1086-1095.

3. Richardson PG, Xie W, Mitsiades C, et al. Single-agent bortezomib in previously untreated multiple myeloma: efficacy, characterization of peripheral neuropathy, and molecular correlations with response and neuropathy. J Clin Oncol. 2009;27:3518-3525.

4. Moreau P, Pylypenko H, Grosicki S, et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomized, phase 3, non-inferiority study. Lancet Oncol.

2011;12:431-440.

5. Bringhen S, Larocca A, Rossi D, et al. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood. 2010;116:4745-4753.

6. Mateos MV. Management of treatment-related adverse events in patients with multiple myeloma. Cancer Treat Rev. 2010;36(suppl 2):S24-S32.

7. Tariman JD, Love G, McCullagh E, et al. Peripheral neuropathy associated with novel therapies in patients with multiple myeloma: consensus statement of the IMF nurse leadership board. Clin J Oncol Nurs. 2008; 12(3 suppl):29-36.

8. Thalidomide [package insert]. Summit, NJ: Celgene Corporation; February 2007.

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NOTES

Value-Based Care in Multiple Myeloma

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About the Association for Value-Based Cancer Care AVBCC is the fastest growing national specialty organization dedicated to improving the care of cancer patients and their quality of life, by discussing, considering, and evaluating the value equation as it relates to new and existing cancer therapies. This organization, which currently consists of over 300 members, was established to provide a network for payers and oncology healthcare professionals to interact and network in order to promote optimal care for patients and their families. ____________________

Mission The mission of AVBCC is to provide a forum for payers, providers, and the entire oncology team to consider and evaluate the cost-value issues particular to cancer treatments and its impact on patient care and outcomes. This unique focus is achieved through discussions and collaborations with those involved in evaluating therapies, treating patients, and paying for care. ____________________

Vision The vision of AVBCC is to provide a unique forum for all stakeholders to discuss, consider, and evaluate the cost-value issues particular to new cancer therapies, as it relates to all cancer patients so they may benefit with optimal outcomes.

AVBCC411

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September 2011

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