Comparison of Adverse Effects of Two Mobilization Regimens for Autologous Hematopoietic Cell Transplant in Multiple Myeloma

Background:

Autologous hematopoietic cell transplantation (HCT) is a standard of care after induction therapy for multiple myeloma (MM). Hematopoietic progenitor cell (HPC) mobilization typically uses G-CSF with or without the CXCR4 antagonist plerixafor (P). Although P has been shown to increase the effectiveness of mobilization, it can be associated with side effects; most commonly GI upset. Due to its high cost, our HPC collection algorithm was updated in an effort to reduce the use of P. The criteria for initiating P became more stringent and far fewer patients were initiated on P prior to their first session of HPC collection apheresis. Prior to October 2017, patients were initiated on P if any 1 of the following criteria were met: age>60 years, prior treatment with melphalan or other alkylating therapy, prior treatment with lenalidomide >2 cycles, extensive bone marrow disease, or platelet count <100K. Starting October 1, 2017, patients were preemptively initiated on P prior to first collection only if all 3 of the following criteria were met: age > 65 years, lenalidomide > 6 cycles, and platelet count < 100K. However, P was added after the first apheresis session if HPC yield was unsatisfactory (<2 x 10^6/kg CD34+ cells). In this study, we analyzed whether a P sparing mobilization regimen led to fewer overall adverse events.

Methods:

We retrospectively collected HPC mobilization data on non-chemo primed patients undergoing HCT for MM from 1/12014 to 12/31/2020. We determined the number of patients mobilized with P, number of mobilization failures (patients requiring repeat mobilization), and number of patients who failed to proceed to transplant. We also determined the number of patients who experienced clinically significant diarrhea or headache. This was defined as diarrhea or headache requiring pharmacologic intervention. Fisher's exact test was used to compare variables in patients undergoing mobilization prior to versus after 10/1/2017. All tests were two-sided and p-values of 0.05 or less were considered statistically significant.

Results:

Two-hundred and twenty-four patients underwent HPC mobilization from 1/1/2014 to 9/30/2017 and 255 patients underwent mobilization after algorithm change from 10/1/2017 to 12/31/2020. As anticipated, the protocol change decreased the number of patients receiving P prior to their first apheresis session. 89% received P prior to the first apheresis session before the change while 14% received this initial dose of P after the change. The number of patients experiencing clinically significant diarrhea decreased from 9.4% to 3.1% with the new P sparing algorithm (p = 0.006). There was no significant difference in patients who experienced headache between the two periods(2.2% pre to 3.1% post, p = 0.59). All patients proceeded to transplant and there was no significant change in the number of mobilization failures (2.2% pre to 3.9% post p = 0.43).

Conclusion:

Changes to our institutional HPC mobilization algorithm led to a substantial decrease in the use of preemptive P prior to day 1 of collection by design. Patients undergoing the P sparing mobilization regimen had significantly reduced clinically significant diarrhea. There was also no significant increase in mobilization failure with the P sparing regimen. Given the recent generic approval of P, and associated cost decrease, we anticipate that many institutions will be evaluating their mobilization algorithms and increasing their use of this drug. The potential for increased adverse events associated with P should be considered when designing these algorithms.

Sauter:Affimed: Research Funding; Gamida Cell: Consultancy; Cargo Therapeutics: Research Funding; Ono Pharmaceuticals: Consultancy; Actinium Pharmaceuticals: Research Funding; Kite/a Gilead Company: Consultancy; NKARTA: Research Funding; GSK: Consultancy; Celgene/BMS: Consultancy; Sanofi-Genzyme: Research Funding; MorphoSys: Consultancy; Juno Therapeutics: Research Funding; Celgene/BMS: Research Funding; Karyopharm Therapeutics: Consultancy; NKARTA: Consultancy; Bristol-Myers Squibb: Research Funding; Precision Biosciences: Research Funding; Ipsen Biopharmaceuticals: Consultancy; CSL Behring: Consultancy; CRISPR Therapeutics: Consultancy; Syncopation Life Sciences: Consultancy. Khouri:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Consultant; GPCR Therapeutics, Inc.: Honoraria; Prothena: Honoraria; Legend: Membership on an entity's Board of Directors or advisory committees.