ONCOLOGY. Vol. 24 No. 11

Pages: 1 2 3

REVIEW ARTICLE

Multiple Myeloma in the Elderly: When to Treat, When to Go to Transplant

By Jean-Luc Harousseau, MD¹ | October 25, 2010

¹ Director, Professor of Hematology, University of Nantes, Nantes/Saint Herblain, France

Current Role of HDT Plus ASCT

The great majority of randomized trials comparing HDT plus ASCT and conventional-dose chemotherapy have recruited patients up to 65 years of age; this explains the age limit for ASCT.[3] However, ASCT is feasible in patients older than 65 years, at least in selected patients with good performance status and no severe comorbidities. The Arkansas group even stated that age was not a biologically adverse parameter and should not constitute an exclusion criterion for ASCT.[41] However, the overall toxicity is higher in patients over 70 and the dose of 200 mg/m2 is too toxic for this population.[42] For this reason, the Italian group has proposed 2 to 3 courses of melphalan(Drug information on melphalan), 100 mg/m2, supported by ASCT[43] and has demonstrated that this semi-intensive approach was superior to conventional chemotherapy with MP in patients aged 50 to 70 years, including in patients aged 65 to 70 years.[44] However, using the same regimen, the IFM failed to confirm this finding. In the three-arm randomized IFM trial 99606 for patients aged 65 to 75 years, the above regimen yielded a higher response rate and CR rate than MP, but PFS and OS were not significantly better; moreover, the MPT regimen was significantly superior both to MP and to melphalan plus ASCT.[9] This discrepancy between the results of the Italian and French studies might be explained by the inclusion criteria, since patients aged 70 to 75 years were included in the French study but not in the Italian one. Still, in light of these results, the use of ASCT in patients older than 65 years, even in conjunction with reduced dosages of melphalan, should not be proposed outside of a clinical trial.

However, there are two other possible explanations for the poor PFS in the IFM 99-06 study:

• Only 65 % of patients received the two planned transplants, and in the majority of patients who dropped out, the reason was either complications of induction treatment with chemotherapy or progression.

• Despite a high percentage of patients with VGPR or better, relapses were rapid in the absence of maintenance treatment.

The use of novel agents in combination with intermediate-dose melphalan might improve results by increasing the efficacy/toxicity ratio of induction treatment and by delaying relapses with post-ASCT consolidation/maintenance. The Italian group recently reported results obtained with such an approach.[45]

Reference Guide

Therapeutic Agents
Mentioned in This Article Bortezomib(Drug information on bortezomib) (Velcade)
Dexamethasone(Drug information on dexamethasone)
Doxorubicin(Drug information on doxorubicin)
Lenalidomide (Revlimid)
Melphalan (Alkeran)
Prednisone
Thalidomide(Drug information on thalidomide) (Thalomid)

Brand names are listed in parentheses only if a drug is not available generically and is marketed as no more than two trademarked or registered products. More familiar alternative generic designations may also be included parenthetically.

Four cycles of bortezomib combined with doxorubicin and dexamethasone (PAD regimen) were administered in 102 patients aged 65 to 75 years. The rate of CR plus VGPR was 58%. Because the induction treatment was effective and well tolerated, 90% of patients received the first ASCT and 83% received the second. After ASCT, patients received lenalidomide consolidation/maintenance therapy, and the final rate of CR plus VGPR increased to 78%, with very encouraging 2-year PFS and OS rates of 69% and 86%, respectively.

Patient selection was probably biased, and patients in poor general condition or with severe comorbidities were certainly not included; it is noteworthy that only 12% of patients had International Staging System stage III disease. Nonetheless, these results show that in the elderly, there is probably a subgroup of patients who may benefit from intermediate-dose melphalan plus ASCT in combination with novel agents.

This finding is particularly important at a time when the place of ASCT in frontline therapy is again being debated even for younger patients.[3] Results obtained with novel agents in patients who are not candidates for ASCT are good enough to justify randomized trials comparing novel agents with or without ASCT as frontline therapy in younger patients . This implies that although ASCT should not be abandoned too early in fit older patients, its role remains undetermined in the era of novel therapies and it should not be proposed outside of a clinical trial.

Financial Disclosure: Dr. Harousseau serves on the advisory boards and speakers’ bureaus of Celgene and Janssen Cilag.

Pages: 1 2 3

by eman moon | October 30, 2010 1:57 PM EDT

excellent

This article reviewed

Melphalan or No Melphalan: That Is the Question

The Treatment of Elderly Patients With Multiple Myeloma: Is More Better?

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Multiple Myeloma in the Elderly: When to Treat, When to Go to Transplant

Current Role of HDT Plus ASCT

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