Positive Outcomes in Novel Treatments for Elderly Patients with Multiple Myeloma

A retrospective study offered a rare look at treatment outcomes for elderly patients with multiple myeloma (MM) using non-melphalan therapies.

The authors of the study, published in Cancer Medicine, noted that over the last decade, novel non-melphalan treatment regimens for multiple myeloma have led to significant improvements in survival. This effect has been observed for patients of all ages, but most research published to-date has involved younger patients.

Authors explained this is because younger patients tend to be eligible for autologous stem cell transplantation (ASCT), leading them toward non-melphalan regimens compatible with stem cell collection. Meanwhile, older patients with MM are typically ineligible for ASCT and led to melphalan-based therapies because of their low cost.

Authors point out several risks associated with the common melphalan-based treatment of elderly MM populations. First, patients are denied the potential improvement in survival offered by novel therapies. Compared with novel immunomodulators, melphalan is less potent, slower in onset, and more myelosuppressive.

Second, because elderly patients tend to be more frail and exhibit more comorbidities (eg, cardiac, pulmonary, renal, hepatic function), these properties of melphalan can effect efficacy and toxicity.

For the first time in the United States, this study was able to compare the outcomes of doublet and triplet novel agent induction therapies for an elderly MM population.

Investigators retrospectively reviewed the records of 133 consecutive patients over the age of 70 at the time of initial diagnosis with symptomatic MM with at least 1 year of follow-up. After excluding individuals with insufficient treatment information, researchers identified a final sample of 117 patients with a median age of 75 years (range 70—95), all treated at St. Vincent’s Catholic Medical Center (and upon its closure in 2010, at Mount Sinai Hospital) in New York City between 1998 and 2013.

Progression-free survival (PFS) and overall survival (OS) rates were calculated from the first day of induction therapy using the Kaplan-Meier method. The log-rank test was used to make univariate comparisons, and a Cox proportional hazards model was used to conduct multivariate analysis.

Study participants exhibited significant baseline comorbidities, including cardiac (36% of sample), renal (20%; CrCl < 30 mL/min), and pulmonary (5%).

Excluding 4 patients who received corticosteroids alone, 95 of 113 patients (84%) received non-melphalan doublet, triplet, or quadruplet initial therapy.

Treating Multiple Myeloma

During the study period, the median duration of follow-up was 43 months, and the median number of lines of therapy was 2 (range 1—7). The most common salvage regimen at first relapse was RVD (lenalidomide + dexamethasone (RD) + bortezomib; 21.7%).

Impressively, the median OS for all participants was 113 months (95% CI; 70.0—156.3 months).

Outcomes were impressive particularly for patients treated with dose-attenuated RVD (n = 34), with an overall response rate (ORR) of 94%; a complete response or very good partial response (CR + VGPR) of 65%; and a PFS of 36 months.

Only 3 patients treated with RVD (8.8%) experienced toxicities that required unplanned dose attenuations, but none discontinued RVD entirely.

The PFS rate with RVD was significantly greater than the PFS of all other regimens (P = .030), including RD (P = .047).

Authors commented that the results of this study were consistent with previous research performed in Europe, such as the FIRST (Frontline Investigation of Lenalidomide + dexamethasone vs. Standard Thalidomide) phase 3 study that demonstrated significant improvements in PFS and OS for elderly patients with MM treated with non-melphalan- versus melphalan-based therapies.

In fact, even at the lowest end of this study’s 95% confidence interval for overall survival (70.0—156.3 months), these US findings showed marked improvement compared with previous research from Europe and Asia.

The improvement may be explained partly by the fact that 85% of this cohort received planned dose-attenuated therapy (an important consideration for patients over age 70); also, by the ready availability of salvage regimens in the United States.

An important takeaway from this research is that dose-attenuated triplet regimens for elderly MM patients can have outcomes similar to those observed with younger patients treated with full dose RVD, with an unexpectedly low incidence of serious Grade 3 or 4 toxicity.