It needs 20 months average until PD However, high risk

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therapy. Elderly patient (81 year old female: IgGλ + BJPλ, stage IIIb) living far from hospital, can visit only once monthly. After 14 months therapy, she achieved CR when switched from VGPR to maintenance therapy Recently, lenalidomide maintenance therapy improved median progression-free survival (41 vs. 23 months with placebo; hazard ratio, 0.50; P < 0.001) [30]. Therapy for relapsed or refractory multiple myeloma (RRMM) Progressive disease is defined as follows: (1) Above 25 % elevation of M-protein, (2) hypercalcemia: corrected serum calcium >11.5 mg/dL, (3) the absolute increase of free light chain (FLC) must be >10 mg/dL, (4) definite development of new

bone lesions or soft tissue plasmacytomas, (5) decrease in hemoglobin of >2 g/dL, (6) rise in serum creatinine by 2 mg/dL or more, (7) increase of BM myeloma cell above 10 %. Analysis of second primary malignancies (SPM) Another important issue in MM is risk of developing SPMs due to living longer from diagnosis. Population studies show MM patients have increased risk of specific SPMs following initial diagnosis, notably acute myeloid leukemia (AML). Some MM therapeutic agents are particularly associated with elevated risk of SPMs. Melphalan is associated with increased risk of secondary acute leukemia. There were imbalances in SPM incidence, including myeloid and lymphoid leukemias, BV-6 clinical trial with post-transplant lenalidomide maintenance therapy and with MP-lenalidomide. Persistent significant OS benefit with VMP versus MP; 13.3-months increase in median, and MPT versus MP increase 6.6 months [9]. Secondary malignancies and lenalidomide: by summarizing the data to-date, the incidence of all/invasive SPM is significantly increased in Lenalidomide arms, driven by hematologic SPM (P < 0.001). B-ALL, Hodgkin lymphoma is reported in post high-dose melphalan and ASCT setting. Sensitivity analysis Baricitinib (including SPM as an event) demonstrates negligible PFS differences.

The overall benefit–risk profile of lenalidomide in NDMM remains positive [31, 32]. Risk Factors for Secondary Malignancies Treatment with lenalidomide may be treatment duration >24 months, male, age >55 years, ISS stage III, previous DCEP (role of concomittant or previous exposure to alkylators?) induction by univariate and multivariate analysis in IFM 2005. In Japanese SPM Report by JRCMC, retrospective analysis for 325 MM patients from 1998 to 2010 (13 years) showed t-MDS/AML developed 17 (5.2 %) patients. Median time to onset: 52 months in t-AML and months in t-MDS. All the patients with t-AML died in a short time, suspected to be treated with Melphalan, and no patients had been given Lenalidomide. We have to select chemo regimen taking into account the risk of t-MDS/AML [33].

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