Beta blockers may act synergistically when administered with the immunomodulatory drug pomalidomide in the setting of relapsed/refractory multiple myeloma, according to findings from a retrospective study reported in the European Journal of Haematology that associated the addition of beta blocker therapy with prolonged survival.1

These results build on data from a previously published retrospective analysis comparing survival outcomes in patients with multiple myeloma who took beta blockers vs those who did not revealed a lower risk of disease-specific death and overall mortality for those in the former group.2

The aim of this phase 2 study was to investigate the potential impact of beta blocker usage on the progression-free survival (PFS) and overall survival (OS) of patients with relapsed/refractory multiple myeloma who received pomalidomide with weekly dexamethasone. Data related to beta blocker usage were abstracted from patient medical records. Patients were categorized according to whether their on-study beta blocker usage as well as their post-diagnosis beta blocker usage endured for a minimum of 3 months.


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Of the 208 patients enrolled, 26% (n=54) had documented on-trial beta blocker usage of at least 3 months. Thirty-seven percent (n=77) had documented beta blocker usage of at least 3 months any time after the diagnosis of multiple myeloma.

Patient baseline characteristics included a median patient age of 63 years for the overall study group. At the time of study enrollment, the patient subgroup that received at least 3 months of beta blocker therapy while on the study had a significantly higher median age compared with the other patient subgroup (68 vs 61 years; P =.0003). However, a comparison of patient-, disease-, and treatment-related characteristics, including sex, performance status, high-risk disease features determined by fluorescence in-situ hybridization at diagnosis, and the number of previous treatments did not reveal any other significant differences between these 2 subgroups.

The study authors found that the median PFS was significantly longer for the patients who received at least 3 months of on-study beta blocker therapy compared with patients who did not receive a beta blocker during the study period (10.9 vs 6.1 months; P =.0168). Furthermore, the 77 patients who received a beta blocker for at least 3 months following disease diagnosis also experienced a significantly longer median PFS compared with the 131 patients who did not (10.5 vs 5.8; P =.0025). In addition, the median OS for these 77 patients was significantly longer compared with that of the patients who did not have beta blocker intake (107 vs 86 months; P =.0157).

Multivariate analyses adjusted for confounding factors showed that both beta blocker usage (HR, 0.666; 95% CI, 0.417-0.943; P =.02) and the duration of on-study beta blocker usage (HR 0.164; 95% CI 0.035-0.694; P =.01) were significantly associated with PFS and hematologic response.

In their concluding comments, the study investigators cited evidence for β-adrenergic signaling pathway-related regulation of the expression of proinflammatory cytokines and vascular endothelial growth factor (VEGF)-related angiogenesis, and noted that these mechanisms of action overlap in part with those of immunomodulatory drugs such as pomalidomide. Nevertheless, “more studies are needed to further explore the potential interactions of [beta blockers] with [immunomodulatory drugs] and other antiangiogenic targeted agents in myeloma therapy,” they concluded.

Disclosure: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the study.

References

  1. Hwa YL, Lacy MQ, Gertz MA, et al. Use of beta blockers is associated with survival outcome of multiple myeloma patients treated with pomalidomide. Eur J Haematol Published online December 1, 2020. doi:10.1111/ejh.13559
  2. Hwa YL, Shi Q, Kumar SK, et al. Beta-blockers improve survival outcomes in patients with multiple myeloma: a retrospective evaluation. Am J Hematol. 2017;92(1):50-55. doi:10.1002/ajh.24582