Real‐world use of pomalidomide and dexamethasone in double refractory multiple myeloma suggests benefit in renal impairment and adverse genetics: a multi‐centre UK experience

Abstract

Myeloma patients who become refractory to immunomodulatory agents (IMiDs) and bortezomib have poor survival, with limited therapeutic options. Pomalidomide has shown improved survival and good tolerability in this patient cohort in clinical trials, but real world data are scarce. We retrospectively analysed all patients treated with pomalidomide at five UK centres between 2013 and 2016. Of 85 patients identified, 70 had sufficient information for response assessments. Median age was 66 years [40-89], 96·5% were refractory to IMiDs, 72·9% were refractory to both an IMiD and bortezomib and 92·9% were refractory to their last treatment. Of 45 patients with fluorescence in situ hybridization results 64% had adverse risk, 19 patients (22·4%) had an estimated glomerular filtration rate <45 ml/min. Grade ≥3 non-haematological toxicities occurred in 42·4%, and grade ≥3 neutropenia and thrombocytopenia in 38% and 24% respectively, but only 18·8% had dose reductions. The overall response rate was 52·9%. At a median follow-up of 13·2 months, median progression-free survival was 5·2 months [95% confidence interval (CI) 4·150-6·238], and median overall survival was 13·7 months (95% CI 11·775-15·707). No significant difference was seen in response, survival or tolerability by renal function, age or cytogenetic risk. This real-world data support the results seen in published clinical trials.

The efficacy and safety of pomalidomide in relapsed/refractory multiple myeloma in a “real‐world” study: Polish Myeloma Group experience

“…7 In general, results of our study are comparable to other randomized clinical studies including ORR of 39.1% (compared with 31% in MM-003 and 32.6% in MM-010) and real-world studies. 6,7,[11][12][13] We found statistically more effective is treatment with POM/DEX/ BORT but we did not find any differences In conclusion, the real-world Polish cohort of RRMM patients has confirmed that pomalidomide is an active drug in this setting and has demonstrated similar response rates, and OS compared with the phase 3 MM-003, MM-010, and other real-world studies.…”

Tolerability and safety of real‑world use of pomalidomide in patients with relapsed/refractory multiple myeloma

“…POM was used at late-stage RRMM. The median patient age (range) was 72 (58-84) years, which was higher compared with that reported in other real-world or large-scale phase 3 trial data 59 (32-78) years in Sriskandarajah et al (12), 61 (41-82) years in Maciocia et al (13) and 66 (37-88) years in the MM-010 trial (9). In the present study, 85.7% of patients were aged >70 years, which was a higher rate compared with the other studies.…”

Renal failure in multiple myeloma: something new on the horizon

“…However, this analysis showed that patients with moderate RI (defined as CrCl ≥30 to <60 ml/min) had a significantly shorter OS compared to those patients without RI. The discrepancy in OS between the two studies (Siegel et al, 2016;Maciocia et al, 2017) may be due to the small number of patients included in the study by Maciocia et al (2017) not allowing a statistically significant difference to be reached in terms of OS, which, in patients with RI, is half that of those without RI.…”

“…However, this analysis showed that patients with moderate RI (defined as CrCl ≥30 to <60 ml/min) had a significantly shorter OS compared to those patients without RI. The discrepancy in OS between the two studies (Siegel et al, 2016;Maciocia et al, 2017) may be due to the small number of patients included in the study by Maciocia et al (2017) not allowing a statistically significant difference to be reached in terms of OS, which, in patients with RI, is half that of those without RI.Although RI in MM is not even remotely solved, Maciocia et al (2017) have shown that, in clinical practice, we have further weapons, such as pomalidomide, to treat advance stage MM patients with RI. The MM-013 trial, designed for advanced stage MM patients with moderate, severe and endstage RI, demonstrated that pomalidomide is safe at routine doses in all groups of patients, with a similar response rate (Ramasamy et al, 2015).…”

“…In this issue of the British Journal of Haematology , Maciocia et al () provide the first real‐life clinical data regarding the safety and efficacy of pomalidomide administered at the dose of 4 mg or less for 21 days, every 28 days, combined with dexamethasone in patients who had CrCl <45 ml/min. They found that the overall response rate, progression‐free survival and overall survival (OS) were similar between patients with or without moderate RI (48% vs. 53%; median 3·7 months vs. 5·2 months, P = 0·882; median 7·4 months vs. 14·1 months, P = 0·586, respectively).…”