Real-world data on Len/Dex combination at second-line therapy of multiple myeloma: treatment at biochemical relapse is a significant prognostic factor for progression-free survival

Abstract

We evaluated progression-free survival (PFS) rate of patients treated with lenalidomide/dexamethasone (Len/Dex), the efficacy of the combination, and the prognostic significance of treatment at biochemical vs. clinical relapse on PFS in 207 consecutive myeloma patients treated with Len/Dex in second line, according to routine clinical practice in Greece. First-line treatment included bortezomib-based (63.3%) or immunomodulatory drug-based (34.8%) therapies; 25% of patients underwent autologous stem cell transplantation. Overall response rate was 73.4% (17.8% complete response and 23.7% very good partial response); median time to best response was 6.7 months. Overall, median PFS and 12-month PFS rate was 19.2 months and 67.6%, respectively. 67.5% of patients had biochemical relapse and 32.5% had clinical relapse prior to initiation of Len/Dex. Median PFS was 24 months for patients treated at biochemical relapse vs. 13.2 months for those treated at clinical relapse (HR:0.63, p = 0.006) and the difference remained significant after adjustment for other prognostic factors. Type of relapse was the strongest prognostic factor for PFS in multivariate analysis. These real-world data confirm the efficacy of Len/Dex combination at first relapse; more importantly, it is demonstrated for the first time outside a clinical trial setting that starting therapy with Len/Dex at biochemical, rather than at clinical relapse, is a significant prognostic factor for PFS, inducing a 37% reduction of the probability of disease progression or death.

Progression with clinical features is associated with worse subsequent survival in multiple myeloma

“…Another Greek study reported on a real-world population of relapsed MM patients uniformly treated with lenalidomide-dexamethasone (Rd) at second line in the current era. 16 The study demonstrated that presence of clinical relapse at treatment initiation negatively impacted post-progression PFS when compared with biochemical relapse. However, an important caveat was the lack of use of triplet regimens which are superior to doublets in relapsed MM.…”

Choosing the Right Therapy for Patients with Relapsed/Refractory Multiple Myeloma (RRMM) in Consideration of Patient-, Disease- and Treatment-Related Factors

“…Biochemical relapse is defined by the IMWG as an increase in serum (absolute increase must be ≥0.5 g/dL) or urine M-protein (absolute increase must be ≥200 mg/24 h) ≥25% from the lowest response value, increased SFLC ratio ≥25% (absolute increase must be >10 mg/dL) from the lowest response value, increase of ≥10% of bone marrow plasma cells or increase in size of pre-existing bone lesions or plasmocytomas (Figure 1) [3]. Patients with confirmed biochemical relapse should receive therapy, especially in case of early, aggressive relapse, rapid increase in myeloma parameters and high-risk cytogenetics [19,33,34]. If the criteria of biochemical or clinical relapse are not met or in case of an asymptomatic, very slow increase in biochemical markers (evolving MM), close monitoring of myeloma parameters at least every 2-3 months is recommended [19,23].…”

“…marrow plasma cells or increase in size of pre-existing bone lesions or plasmocytomas (Figure 1) [3]. Patients with confirmed biochemical relapse should receive therapy, especially in case of early, aggressive relapse, rapid increase in myeloma parameters and highrisk cytogenetics [19,33,34]. If the criteria of biochemical or clinical relapse are not met or in case of an asymptomatic, very slow increase in biochemical markers (evolving MM), close monitoring of myeloma parameters at least every 2-3 months is recommended [19,23].…”

Plateau is a prognostic factor of lenalidomide therapy for previously treated multiple myeloma

“…At the 2014 meeting of the International Myeloma Working Group (IMWG), 9 relapse was subdivided into three categories: (1) clinical relapse, which is defined as reappearance of CRAB symptoms (hypercalcemia, renal impairment, anemia, or bone lesions); (2) paraprotein relapse, which is defined as re‐emergence of serum paraproteins (M protein); and (3) biochemical relapse, which is defined as M protein increases by ≥25% from the minimum value and an absolute level of increase by ≥500 mg/dl; it is recommended to initiate treatment at paraprotein relapse. In addition, recent clinical studies on relapsed and refractory MM (RRMM) have focused on initiating treatment at the first signs of biochemical relapse, resulting in excellent outcomes and suggesting it is important to initiate treatment changes at the earliest stages of disease progression 10 . However, the time to the increase in M‐protein levels is not defined in biochemical relapse, which may include various relapses of different durations from the best therapeutic effect to relapse, although there is currently no consensus recommendation to change therapy at this point.…”