Real-Life Experience with Pomalidomide plus Dexamethasone in Patients with Multiple Myeloma: A Single Center Retrospective Study

Abstract

Objective: Multiple myeloma (MM) is a heterogeneous disease with the uncontrolled clonal proliferation of plasma cells, accounting for approximately 10% of all hematologic cancers . Hence without curative therapy, the treatment aims to improve overall survival.Pomalidomide (POM) is a third-generation immunomodulatory agentPomalidomide can be administered with dexamethasone or in combination with proteasome inhibitors (bortezomib) and monoclonal antibodies (isatuximab, daratumumab). We retrospectively analysed all patients treated with pomalidomide at our centre between 2017 and 2023. Methodology: All patients who had received or were currently receiving treatment with pomalidomide at Ege University Hematology Outpatient Clinic between January 2017 and April 2023 were included. To be included in response assessments, patients had to have measurable disease as defined by International Myeloma Working Group (IMWG) guidelines (Kumar et al, 2016) and have completed at least one cycle of pomalidomide with repeat biomarkers performed. Treatment consisted of 28-day cycles of pomalidomide (taken daily on days 1–21) plus dexamethasone (on days 1, 8, 15 and 22), plus or minus a third agent. Results: A total of 25 patients who received treatment with pomalidomide were identified. Of these, 24 were able to be included in response analyses. Of the remaining 1 patient for whom response could not be assessed,had an anaphylactoid reaction with pomalidomide and did not complete a single cycle of treatment.The analysis includes a total of 23 patients with RRMM, 1 patient with newly diagnosed multipl myeloma who had central nervous system involvement at diagnosis. 23 patients treated with POM-DEX in the lines of therapy subsequent to the second (third to seventh) line. Median patient age at diagnosis was 55 years (range 42–82), 7 (28%) patients were 65 or older than 65 years old. 13 patients were male (54,25%) and 11 were female (45,85%). 6 (25%) patients had International Staging System (ISS) stage I, 5 (20,8%) had stage II, 11 (45,8%) stage III myeloma, respectively (2 patients had not adjusted) stage III myeloma. 79,2 % (n=19)of patients had IgG, 4,2% (n=1) had IgD, 79,2 % (n=19) had kappa and 20,8 % (n=5) had lambda subtype myeloma. Six patients (25 %) had extramedullary disease and 18 (75 %)had lytic bone lesions at diagnosis.Moreover, 12 (%50)patients had received a previous autologous stem cell transplant (single or double). 1 patient had autologous stem cell transplant after pomalidomide therapy. On data cut off (1 August 2023), median survival from initial diagnosis was not reached .Nearly all patients had received at least two previous lines of therapyand, as per guideline, had been exposed both to lenalidomide and bortezomib. Efficacy In a total of 24 patients, the treatment response rate (ORR), including all patients with a partial response or better, was 41.7%. A total of 10 patients gained a partial response (3) or a complete response (7). Median progression-free survival (PFS) was 18,95±5,18 months. Median (IQR) treatment duration was 8 (2-47)months. 2 years OS had adjusted as % 35,4 ±12,8.The most common adverse events were hematologic toxic effects, such as neutropenia (11 patients), anemia (3), thrombocytopenia (1); we also described gastrointestinal symptoms such as diarrhea, infections or sepsis, pneumonia. Conclusion: Multiple myeloma (MM) is a heterogeneous disease with the uncontrolled clonal proliferation of plasma cells, accounting for approximately 10% of all hematologic cancers. Prognosis of patients after a second relapse remains poor, and the treatment is still challenging. According to the phase three study MM-003, pomalidomide in combination with dexamethasone (DEX) was approved as a subsequent line of therapy to the second one by the US Food and Drug Administration and the European Medicines Agency (EMA) in 2013, respectively, showing efficacy in patients with RRMM and previously exposed to both bortezomib and lenalidomide . In this study, we analyzed the efficacy of oral pomalidomide plus dexamethasone regimen in our patients that received more than one cycle of POM-DEX therapy. Although our patients received POM-DEX at an advanced stage of disease the findings from our real-life experience indicate that Poma-D is a safe and well-tolerated regimen with acceptable toxicity. The ORR reported in our study was 41.7% and is better than previous studies (33% in MM-002, 31% in Nimbus, and 32.6% in Stratus). The PFS observed in our cases of 18,95 ±5,18 months is also quite favorably comparable with that of previously mentioned trials (which described median results of 4.0–4.6 months). Nowadays triplet regimens are widely considered the standard of care in myeloma. Though the efficacy of POM-DEX, should not be underestimated for all those patients in which three-drug regimens are not indicated (because they are frail or very elderly, or with significant adverse effects related to proteasome inhibitors).