Clinical Benefit of Long-Term Disease Control with Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients

Abstract

Background: We retrospectively analysed relapsed/refractory MM (RRMM) patients treated with pomalidomide and dexamethasone (PomaD) either in real life, or previously enrolled in an interventional (STRATUS, MM-010) or currently enrolled in an observational study (MM-015) to provide further insights on safety and tolerability and clinical efficacy. Methods: Between July 2013 and July 2018, 76 RRMM patients (including 33 double refractory MM) received pomalidomide 4 mg daily given orally on days 1–21 of each 28-day cycle, and dexamethasone 40 mg weekly (≤75 years) or 20 mg weekly for patients aged > 75 years. In nine patients a third agent was added to increase the response: Cyclophosphamide (in two fit patients) or clarithromycin (in seven frail patients). Patients received subcutaneous filgrastim as part of the prophylaxis regimen for neutropenia. Results: A median number of six (range 2–21) PomaD cycles were given. The regimen was well tolerated with grade 3–4 haematological and non-haematological adverse events in 39 (51%) and 25 (33%) patients, respectively. In patients who developed serious AE, pomalidomide dose reduction (11%, 14%) or definitive discontinuation (18%, 23%) were applied. All patients have been evaluated for response within the first two cycles. The disease control rate (DCR), i.e., those patients that had a response equal or better than stable disease (≥ SD), was high (89%), with 44% overall response rate (ORR) after six cycles. The achieved best responses were complete remission (CR, 5%), very good partial remission (VGPR, 4%), partial remission (PR, 35%), minimal response (MR, 7%), and stable disease (SD, 38%). After a median follow up of 19.6 months, median progression free survival was 9.4 months, and overall survival (OS) was 19.02 months. Univariate analysis showed that double refractory patients, or who received more than three previous lines had shorter PFS. At 18 months, regardless of the depth of response, patients with a disease control of at least six months, defined as maintenance of a best clinical and/or biochemical response to treatment for almost six months, had prolonged PFS (35.3% versus 20.6%, p = 0.0003) and OS (81.2% versus 15.9%, p < 0.0001) Conclusions: Our findings indicate that PomaD is a safe and well-tolerated regimen in real-life, associated with prolonged PFS and OS with acceptable toxicity. Moreover, Pd induced disease control in most intensively pre-treated patients and some of them achieved longer PFS than that obtained with the previous treatment.

Daratumumab as Single Agent in Relapsed/Refractory Myeloma Patients: A Retrospective Real-Life Survey

“…Regarding the infectious AEs, compared to other real-life studies, the incidence of grade 3-4 events was lower (31)(32)(33)(34)(35). We can hypothesize that the use of antiviral and antibiotic prophylaxis, together with on demand G-CSF supportive therapy could have been of aid in reducing the incidence of infectious complications, similar to our previous real-life experience with Poma-Dex (44) and KRd regimen (40). The presence of grade 3/4 hematological adverse events was also significant in terms of PFS in univariate analysis.…”

Lenalidomide and Pomalidomide Improve Function and Induce FcγRI/CD64 in Multiple Myeloma Neutrophils

“…For both NDMM and RRMM patients, concomitant medications included agents for thrombo-prophylaxis with low-dose aspirin for low-risk patients and with lowmolecular-weight heparin for high-risk patients [15], and anti-infectious prophylaxis, consisting of Trimetoprim and Sulfametoxazole 800 mg twice daily for two days per week with Acyclovir 400 mg daily. In RRMM patients, secondary prophylaxis with subcutaneous G-CSF was given if the neutrophil count (ANC) was ≤ 1.5 × 10 9 /L, to avoid pomalidomide dosage reduction.…”

“…Pomalidomide is an immunomodulator with multiple activities: immunomodulating, antiangiogenetic and antineoplastic. Pomalidomide appears to inhibit TNF-alpha production, enhance the activity of T cells and natural killer (NK) cells, and enhance antibody-dependent cellular cytotoxicity (ADCC) [13][14][15]. Despite these properties, pomalidomide therapy is characterized by a high incidence of neutropenia and febrile neutropenia, which are also responsible for frequent treatment interruptions or dosage reductions that may compromise the efficacy of the treatment [15][16][17][18][19][20].…”

“…Pomalidomide appears to inhibit TNF-alpha production, enhance the activity of T cells and natural killer (NK) cells, and enhance antibody-dependent cellular cytotoxicity (ADCC) [13][14][15]. Despite these properties, pomalidomide therapy is characterized by a high incidence of neutropenia and febrile neutropenia, which are also responsible for frequent treatment interruptions or dosage reductions that may compromise the efficacy of the treatment [15][16][17][18][19][20]. To establish if neutrophil function is still compromised in RRMM and if pomalidomide or supportive care with filgrastim can affect the expression of FcγRI/CD64 on surface neutrophils, we designed a single-center prospective observational study in double-refractory RRMM patients treated uniformly with PomDex.…”

A Real-Life Survey of Venous Thromboembolic Events Occurring in Myeloma Patients Treated in Third Line with Second-Generation Novel Agents

“…These recommendations were then taken up and confirmed by the 2015 European Myeloma Network (EMN) [ 38 ] and 2017 ESMO guidelines [ 39 ]. Limited data are available about thrombotic risk in patients on treatment with pomalidomie but, as with the other IMiDs, it seems to determine an increased risk of thrombosis [ 17 , 25 , 40 , 41 , 42 , 43 , 44 ]. With regard to the second-generation proteasome inhibitor Carfilzomib, phase III trial ASPIRE, which compares the efficacy of lenalidomide-dexamethasone versus carfilzomib-lenalidomide-dexamethasone, shows a higher incidence of VTE in the three-drugs arm (13% vs. 6%), despite the mandatory use of thromboprophylaxis [ 45 ].…”