Secondary primary malignancies during the lenalidomide–dexamethasone regimen in relapsed/refractory multiple myeloma patients

Abstract

Lenalidomide in combination with dexamethasone (Len‐dex) represents a highly effective treatment in relapsed/refractory multiple myeloma (RRMM) patients. However, an increased risk of secondary primary malignancies (SPMs), including myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) has been described in patients receiving lenalidomide. In order to assess the incidence and features of this complication, we reviewed 195 patients with RRMM treated with Len‐dex at our institution. The median follow‐up time from diagnosis of MM was 73 months (10–234 months) and from initiation of Len‐dex was 19 months (1–104 months). The median duration of Len‐dex for all patients was 7.8 months (range 1–90 months). The incidence rate (IR) for all SPMs from start of Len‐dex was 2.37 per 100 patient‐years, which reflected an IR of 1.29 for MDS/AML and 1.08 for nonhematologic malignancies (NHM). MDS was the most common SPM noted. The cumulative IR of SPM at 5 years was 1.54% from the time of MM diagnosis and 5.24% from starting Len‐dex. Multivariable cumulative incidence of SPM analysis identified older age (P = 0.005) and prior number of regimens (P = 0.026) as adverse risk factors. We found more concomitant G‐CSF use (P = 0.029) in patients with MDS/AML, however, causal association is not clear. The progression‐free survival after Len‐dex was the longest for patients in MDS/AML group, and the 5‐year overall survival did not differ among groups. Although the rate of SPM was relatively low with Len‐dex, concomitant G‐CSF should be used judiciously and patients receiving this regimen should be observed for the development of this complication.

Increasing therapy‐related myeloid neoplasms in multiple myeloma

“…Previous studies have described an increased risk of SMPs in MM patients, notably the development of MDS/AML . The association between the development of TRM neoplasms and the treatment with lenalidomide in patients with MM is a matter of debate, with contradictory results reported . Differences in the design of these studies might account for those discrepancies, with the lack of SPMs incidence/follow‐up in those cases in which lenalidomide was discontinued, as the major limitation in the clinical trial setting.…”

“…According to our data, complex karyotype is the most frequently alteration in TRM malignancies in patients treated for a previous MM. In another population‐based study focused on SPMs during the lenalidomide‐dexamethasone regimen in relapsed/refractory MM patients 5 out of 6 patients who developed a therapy related AML/MDS had complex cytogenetics . With regard to survival, in a previous large population‐base study of MM patients the median time of survival after diagnosed AML/MDS was 2.4 months ,.…”

“…Recently, it has been suggested a relationship between SPMs and treatment with lenalidomide . However, reports regarding TRM neoplasms in lenalidomide treated patients are uneven . The aims of this study, performed in a well annotated series of MM patients, with a prolonged follow‐up, were as follows: i) to analyse the incidence and characteristics of SPMs in the whole cohort comparing its data with a general population registry; ii) to determine differences in SPMs occurrence with the emergence of new therapies; iii) to test for SPMs risk factors within a competitive risk model.…”

Cardiac ALL: Most Unusual Occurrence of Lenalidomide-associated Acute Lymphoblastic Leukemia with Subsequent Cardiac Involvement

“…Several studies, including an analysis of pooled data from 11 clinical trials of lenalidomide-based therapy involving 3846 patients with relapsed refractory multiple myeloma (RRMM) reported an incidence ratio (IR) of 3.36 for all SPMs and 2.08 for all-invasive hematological malignancies [11]. Another retrospective study with 195 patients showed the incidence of myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) as 1.29 and 1.08, respectively [12-13]. The overall median time of diagnosis of SPMs is 28 months for hematological and 15 months for solid tumors [13-14].…”

Rapid Evolution of a Myelodysplastic Syndrome in a Case of Multiple-Myeloma: Therapy Related or Not?

“…In the era of immunomodulating drugs (imids) and especially lenalidomide, Reece and Goswami reported MDS/AML in 2.6% of patients treated with lenalidomide for refractory/relapsed MM, at a median of 76 months from the time of MM diagnosis [6]. An even longer delay was reported very recently by the same group in a single institution, with a median time from diagnosis to MDS/ AML appearance of 6.7 years [7]. occurred very rapidly, barely 2 years after auto-SCT.…”