Abstract
Introduction
Multiple Myeloma (MM) is a hematologic malignancy characterized by proliferation of clonal plasmacells in the bone marrow and sometimes extramedullary sites which inevitably tend to relapse. Patients with relapsed/refractory MM (R/R MM) who are treated with conventional drugs as immunomodulating agents (IMiDs) and proteasoma inhibitors (PIs) have a poor survival. Based on the results of MM 003 phase III randomised trial, pomalidomide in association with dexamethasone has shown to improve R/R MM outcome.
We conducted a single-center real life-based observational and pharmacological analysis to investigate the efficacy and tolerability of pomalidomide in a group of patients with R/R MM previously exposed to IMiDs and PIs.
Method and Materials
We included 34 patients (females 21) treated with pomalidomide (POMA) from January 2015 to May 2018 at the Hematology Department of "Santo Spirito" Hospital in Pescara, Italy. All patients were diagnosed by R/R MM according to IMWG guidelines and were classificated using ISS criteria. Prognostic cytogenetic value was identified by FISH analysis. POMA was administred at the oral daily dose of 3-4 mg (days 1-21) in combination with oral dexamethasone (days 1,8,15,22) at the dosage of 20 mg/day. Adverse events were evaluated according to the common terminology criteria for adverse reactions (CTCAE version 4.0). Overall survival (OS) and progression free survival (PFS) were designed according to Kaplan-Myer method. The adherence to therapy was determined using 'received daily dose/prescribed daily dose' method (RDD/PDD). Statistic analysis were conducted with GraphPad Prism 7.0; p values ≤ 0.05 were considered statistically significant.
Results
The clinical and biological characteristics of 34 patients are described in Tab.1.
The median follow up after POMA therapy was 5 months (range, 1-32); at the end of this period 12 patients had completed at least 6 cycles of therapy (range, 1-21). Overall response rate (ORR) was 24%: 4 complete remission (CR), 3 very good partial response (VGPR), 1 partial response (PR); moreover 6 patients (18%) achieved a minimal response (MR). Clinical benefit rate (CBR) was 74%: ORR plus 6 MR and 11 stable disease (SD). At time of this report 12 patients (35%) are living. Among living patients, 4 are now receiving other treatments and 8 are still under POMA treatment: 4 are in CR, 1 is in PR, 1 in MR and 2 in SD. Median OS of all patients was 10 months, whereas median PFS was 6 months (Fig.1,A-B). Median PFS was notably lower in high cytogenetic risk patients (4 months) as compared to the PFS of standard cytogenetic risk patients (16 months) (p= 0.02) (Fig.1,D). Patients treated with at least 4 previous lines of therapy had a median PFS of 5 months, while those receiving until 3 previous lines of therapy had a median PFS of 24 months (p= 0.01) (Fig.1,C). Patients receiving a drug regimen lenalidomide-based as last treatment before starting POMA didn't show significant difference in PFS from those receiving other treatments (4 months vs 6 months) (p=NS). During treatment with POMA, 22 patients (65%) showed adverse drug reactions (ADRs) for a total of 77. Seventy-four ADRs were ≥ 2 grade. Forty nine ADRs (63%) were hematological and 43 ADRs (56%) occurred in the first 3 months of therapy. In particular Twenty-two of them occurred within the first month of therapy. Thirty two cases of ADRs (41%) were successfully managed with simple delay of treatment. As consequence, the adherence to therapy was not optimal (78%). However only 9 (12%) of the total ADRs were cause of end of treatment.
Conclusions
Despite the low sample size and short follow-up, our real life analysis contributes to show that pomalidomide therapy is a favorable option for patients with R/R MM, leading to good responses in terms of OS and PFS. The best results were obtained when POMA treatment was utilized at first relapses and in particular in patients with favorable genetic profile. About the safety, despite the frequent hematological toxicity, ADRs can be quite easily managed to allow few interruptions of the treatment and improve the adherence.
No relevant conflicts of interest to declare.
