Realistic Lenalidomide Dose Adjustment Strategy for Transplant-Ineligible Elderly Patients with Relapsed/Refractory Multiple Myeloma: Japanese Real-World Experience

Abstract

Lenalidomide is an immunomodulatory drug administered orally in the treatment of multiple myeloma. Some elderly patients require a reduced lenalidomide dose because of comorbidities and/or adverse events. This study investigated the actual dose of lenalidomide in elderly patients, finding that most received reduced (5-10 mg) doses. The most common reasons for dose reduction were renal dysfunction (54% of patients), fatigue (grade ≥3; 20%), hematologic disorder (grade ≥3; 14%), and rash (grade ≥3; 9%). Their median time to progression was 11.8 months and their median overall survival was 39.2 months. The overall response rate was 73%, including 17% with a complete response, 19% with a very good partial response, and 37% with a partial response. These results showed that, contrary to western countries, most patients were treated with a reduced dose of lenalidomide in Japan. However, it is suggested that continued treatment with a tolerable dose may yield favorable outcomes.

<p>Updated Perspectives on the Management of Multiple Myeloma in Older Patients: Focus on Lenalidomide</p>

“…As high as 16% of patients developed a second malignancy during treatment. 33 This singleinstitution, retrospective study indicates that many patients have challenges tolerating the recommended doses of lenalidomide outside of a clinical trial setting, and outcomes for lower dose lenalidomide were similar to higher dose lenalidomide in this limited cohort. Median OS was also significantly better for the VRd arm (75 months) than the Rd arm (64 months) (HR 0.709, 95% CI 0.524-0.959; P= 0.025).…”

“…Several studies reported an increased risk of developing a second primary malignancy after treatment with lenalidomide in a melphalan-containing regimen or as maintenance post-ASCT. 20,25,33,46 A pooled analysis of 11 clinical trials of relapsed multiple myeloma treated with lenalidomide regimens showed an incidence rate of 3.62 with hematologic/ solid tumors having an incidence rate of 2.08 (comparable to background incidence). An analysis of MM-009 and MM-010 showed an incidence rate of 3.98; excluding nonmelanoma skin cancers, the incidence rate for hematologic/ solid cancers was 1.71 on Rd.…”

“…44 As exemplified in the "real world" studies included here, many older adults are not able to tolerate the full dose of lenalidomide recommended in clinical trials, and dose adjustments are frequently needed. 33 A recently published comprehensive treatment algorithm for newly diagnosed older adults with multiple myeloma suggested treatment based on breakdown by IMWG Frailty score. Recommended lenalidomide-based regimens included Dara-Rd and VRd for fit patients; Rd-R, Rd, or vrd-lite for intermediate-fit patients; rd for frail patients.…”

Very-Low-Dose Lenalidomide for Elderly and/or Frail Multiple Myeloma Patients: Lower Might Be Better

“…In this issue of Acta Haematologica , Nakaya et al [5] report the efficacy and less toxic profile of low-dose (5- 10 mg) lenalidomide for the treatment of refractory myeloma. With the limitations of a retrospective observation, the investigators demonstrated that most patients, whose median age was 76.5 years (67-88), were treated with low-dose lenalidomide (5-10 mg) as a starting dose, and continued the same dose while being closely monitored for adverse events.…”

“…If the myeloma response was not optimal, the dosage could be titrated to achieve the desired response up to the maximum tolerated dose. However, Nakaya et al [5] showed that there is no survival benefit with a dose escalation greater than 10 mg. Future studies need to address which strategy is more valuable, a dose-escalation for optimal response or a low-dose maintenance for good quality of life.…”