Lenalidomide in relapsed and refractory multiple myeloma disease: feasibility and benefits of long-term treatment

Abstract

Lenalidomide in combination with dexamethasone is an effective and well-established treatment of relapsed or refractory multiple myeloma (rrMM) disease. Due to the scarcity of reports assessing benefit and risk of long-term lenalidomide treatment in non-selected rrMM patients, we retrospectively analysed the long-term outcome in patients with rrMM treated with lenalidomide and dexamethasone. Sixty-seven patients (pts) who were treated with lenalidomide/dexamethasone for rrMM in the approved indication from 2007 to 2011 were included in this retrospective, single-centre analysis. Kaplan-Meier survival estimates were compared between total population, patients on lenalidomide for more than 12 months (mo) and patients discontinuing therapy earlier than 12 months. Median overall survival (OS) of the total patient population was 33.2 mo. OS of pts treated beyond 12 mo was 42.9 mo compared to 20.2 mo (p = 0.027) for pts stopping lenalidomide earlier than 12 mo for other reasons than progression disease (PD). OS of pts >12 mo on lenalidomide treatment did not significantly differ between pts who had received previous autologous transplantation, allogeneic transplantation or conventional therapy. Main non-hematologic toxicities were infections of grade 3/4 in 25 % and thrombembolic events of all grades in 18 % of patients. To the best of our knowledge, this is the first report on feasibility and efficacy of long-term lenalidomide treatment in a non-selected patient cohort. OS of pts >12 mo on lenalidomide is superior when compared to pts discontinued earlier for reasons other than PD. Our data confirm the current use of lenalidomide as a continuous long-term treatment strategy.

Prolonged Duration of Therapy Is Associated With Improved Survival in Patients Treated for Relapsed/Refractory Multiple Myeloma in Routine Clinical Care in the United States

“…These were based on subgroup analyses of large prospective trials in which treatment was given until progression or, alternatively, on small single-institution experiences. [8][9][10][11][12] In 1 study of 50 patients, those treated for > 3 years had a longer median TTP compared with those treated for 2 to 3 years, regardless of the response rate. 10 In another small retrospective study of 67 patients, OS and the overall response rate were significantly better for patients treated with lenalidomide and dexamethasone for > 12 months compared with patients who stopped treatment at < 12 months for reasons other than progression.…”

“…10 In another small retrospective study of 67 patients, OS and the overall response rate were significantly better for patients treated with lenalidomide and dexamethasone for > 12 months compared with patients who stopped treatment at < 12 months for reasons other than progression. 11 However, these studies varied in the extent to which they controlled for patient and disease factors and treatment exposure at baseline and over time-all aspects that can affect OS. Some analyses did not account for selection 8 and/ or survival 10,12 bias.…”

“…Others adjusted for baseline confounders but did not account for selection bias over time or survival bias. 11 Some included landmark analyses 8 or time-dependent multivariate Cox regression models. 9 However, with these traditional regression methods, including Cox regression models with time-varying covariates and landmark analyses, the possibility exists that the results could be biased in the presence of a time-dependent exposure (continuation of therapy) and time-varying confounders.…”

Efficacy and safety of lenalidomide treatment in multiple myeloma (MM) patients—Report of the Polish Myeloma Group

“…The above mentioned model was on the borderline of statistical significance, however the fact that the number of LEN cycles was a parameter with the strongest impact on treatment response achievement (p = 0.026919) pays attention. In studies by Zago and Mele, LEN + DEX treatment used over 12 months significantly increased ORR [7,15]. Moreover, Harousseau revealed that LEN + DEX treatment continuation increased best response rate [16].…”

“…Therefore, similarly to treatment response achievement analysis, the number of LEN treatment cycles was a substantial OS-determining factor. In studies by Zago, OS in patients receiving treatment >12 and <12 months was 43 months and 20 months, respectively; and the obtained difference was statistically significant [15]. In addition to the number of previous lines of treatment and disease stage according to DurieSalmon staging system, San Miguel demonstrated that ␤-2 -M levels and LEN + DEX treatment cycles had important impact on patients' survival time [19].…”