Use of Alkylating Agents Among Patients with Multiple Myeloma in a National Registry, 2006-2008.

While alkylating agents were among the earliest treatments for multiple myeloma, newer therapies have been available for several years. Here we describe patterns of use and effectiveness of alkylators in the modern landscape of myeloma treatment, based on a nationwide registry of recently diagnosed patients.

The “Patient Registries at Slone: Myeloma” is a national disease-based observational registry conducted by Boston University. All patients with myeloma diagnosed within 4 months of enrollment were eligible for inclusion. Subjects enrolled by mail or over the internet; information on treatment, clinical events, and quality of life was obtained by questionnaire and from medical record review at baseline and at six-month intervals. There were 342 patients with multiple myeloma residing in 43 states who were enrolled from June 2006-October 2008 and completed at least a baseline questionnaire. The median length of follow-up was 8 months after diagnosis (range 0.5-24).

Alkylators were used as initial treatment in 26 patients (8%), as second-line treatment in 14 (4%), and as part of a transplant regimen in 76 (22%). Patients who received alkylators as initial or second-line therapy tended to be older (median age, 69 vs. 60 years, p<0.0005), and the combined prevalence of use was 17% among patients who did not have prescription drug insurance, compared with 11% among those who did (p=0.36). The prevalence of first-line use was 12% among patients diagnosed in 2006, 9% in 2007, and 4% in 2008 (p=0.09). Further results are confined to 34 of the 40 first or second-line alkylator recipients for whom medical records were available. The regimens used are shown in the table; the majority of patients received regimens that included melphalan. The median duration of initial therapy

was 3 months (range 0.5-15); 6 patients (24%) had at least a partial response. Ten patients were still on treatment at the end of follow-up; in 15 (60%), alkylator therapy was changed to another regimen (11) or stopped without new therapy during the follow-up period (4), including 3 due to insufficient response and 5 due to toxicity. The new regimens were thalidomide-based in 2 patients, bortezomib-based in 3, bortezomib+lenalidomide in 1, dexamethasone without novel agents in 2, and 3 patients went directly to autologous stem-cell transplant. Second-line therapy with alkylators was initiated due to insufficient response from the previous regimen in 2 patients, because of side effects in 5, and for cost reasons in 2. The median duration was 2 months (range 0.5-12, with 4 patients still on treatment), and 4 (44%) had a partial or better response. The immediately preceding regimen was thalidomide-based in 5 patients, lenalidomide-based in 1, and bortezomib-based in 3; the median number of previous regimens was 2 per patient (range, 1-4). The median duration of previous therapy was 4 months (range 0.5-9).

The present population-based results indicate that in the modern era of myeloma treatment, the most prevalent use of alkylating agents is as conditioning for stem cell transplants; the drugs are also still used for initial treatment, mostly in combination with novel agents, although the prevalence was low overall and continued to decline during 2006-2008. Patients who received alkylators for initial or second-line therapy were older and the agents appeared to be somewhat more commonly used among those who did not have prescription drug insurance. The data suggest that there continues to be a useful role for alkylating agents as initial therapy, particularly for myeloma patients who are not transplant candidates, and occasionally as an early replacement for novel agents that prove ineffective or excessively toxic in individual patients. With a relatively short duration of follow-up, there was little information on the use of alkylators in the relapsed setting, where their high level of anti-myeloma activity might be expected to lead to more use.

Van Bennekom:Cephalon: Research Funding; Celgene: Research Funding; Millennium: Research Funding; Genentech: Research Funding. Anderson:Cephalon: Research Funding; Celgene: Research Funding; Millennium: Research Funding; Genentech: Research Funding. Raje:Celgene: Research Funding; Novartis: Research Funding; AstraZeneca: Research Funding. Anderson:Celgene: Consultancy, Research Funding, Speakers Bureau; Millennium: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Research Funding, Speakers Bureau. Kaufman:Cephalon: Research Funding; Celgene: Research Funding; Millennium: Research Funding; Genentech: Research Funding.