Real-World Blood Counts in Patients Treated with Venetoclax for Relapsed or Refractory CLL/SLL

Background: Venetoclax administered as monotherapy or in combination with other agents is a standard-of-care treatment for patients (pts) with CLL/SLL. Although neutropenia is a well-documented adverse event in pts treated with venetoclax, little is known about the severity of this or other cytopenias in pts with relapsed or refractory disease. This study aims to evaluate venetoclax-associated cytopenias and their treatment impact among this population.

Methods: This single-institution, retrospective study used an institutional CLL database to identify pts with relapsed/refractory CLL/SLL who received at least 30 days of venetoclax. Laboratory and clinical data were extracted from electronic medical records and paired t-tests were conducted to compare complete blood count (CBC) data dated before, during, and after venetoclax administration. Multivariate analyses evaluated the relationship between blood counts and clinical outcomes. Median blood counts were reported at 3-month intervals for pts who received venetoclax for up to 1 year.

Results: A total of 71 pts received venetoclax for relapsed/refractory CLL/SLL for a median of 8.2 months (range 1.1 - 48.4 months). Prior treatment frequently included a Bruton's tyrosine kinase inhibitor (BTKi; 70%), and/or chemoimmunotherapy (68%). Three pts (4%) received prior treatment with a phosphoinositide 3-kinase inhibitor. Pts received a median of 2 lines of therapy (range 1-7) prior to starting venetoclax, which was administered in combination with a CD-20 antibody (58%) for a median of 13.3 months, in combination with a BTKi (14.3%) for a median of 6.0 months, or as venetoclax monotherapy (28%) for a median of 11.2 months. Four pts (6%) discontinued venetoclax due to neutropenia, while another 4 continued therapy after dose reductions were made specifically to address neutropenia. Thirteen pts (18.3%) received granulocyte colony-stimulating factors (G-CSF) while on venetoclax and 21.0% of all absolute neutrophil count (ANC) lab values during treatment met criteria for grade ≥3 neutropenia. There was a statistically significant decrease in mean neutrophil count at the end of venetoclax treatment (mean difference = 1.00362 10³/µL, p-value = 0.0002). A statistically significant reduction in mean neutrophil count was not sustained after venetoclax was stopped at a median follow-up of 35.2 months (range 2.8 - 102.7 months). Statistically significant changes in hematocrit and platelet count were also not observed, however the median hematocrit tended to increase with treatment from 35.0% at 0-30 days (n = 71) to 37.6% at 3 months (n = 65), 40.0% at 6 months (n = 58), 40% at 9 months (n = 45), and 41.0% at 1 year (n = 41). Median platelet counts were relatively stable and ranged from 125 10³/µL to 146 10³/µL over the same 1-year period.

Conclusion: Venetoclax is associated with decreased neutrophil count in patients with relapsed or refractory CLL/SLL, which may result in the use of G-CSF, dose reductions, or even drug discontinuation. This effect does not appear to be sustained after venetoclax is stopped. Consistent with the known therapeutic effect of venetoclax, hematocrit appears to trend up while platelet counts remain relatively stable in patients on treatment.

Lynch:TG Therapeutics, Incyte, Bayer, Cyteir, Genentech, SeaGen, Rapt, Merck, Janssen: Research Funding; Merck: Honoraria; SeaGen, Foresight Diagnostics, Abbvie, Janssen: Consultancy. Di:BeiGene: Consultancy, Research Funding; Schrodinger, Inc.: Research Funding. Poh:Dren Bio: Research Funding; Ipsen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Acrotech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astex: Research Funding; Seagen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding. Smith:KITE pharma: Consultancy; Millenium/Takeda: Consultancy; Lumanity: Consultancy; Merck Sharp and Dohme Corp: Research Funding; Genentech: Consultancy, Research Funding; abbvie: Consultancy; ADC therapeutics: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; Coherus Biosciences (spouse): Consultancy; Kymera Therapeutics: Research Funding; Ignyta (spouse): Research Funding; Incyte: Consultancy, Research Funding; Karyopharm: Consultancy; Bayer: Research Funding; BMS (spouse): Research Funding; De Novo Biopharma: Research Funding; Enterome: Research Funding; Epizyme: Consultancy. Till:Bristol Myers Squibb: Research Funding; Mustang Bio: Consultancy, Patents & Royalties, Research Funding. Gopal:Merck: Consultancy, Honoraria, Research Funding; I-Mab bio: Research Funding; IgM Bio: Research Funding; Takeda: Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Astra Zeneca: Research Funding; Agios: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Research Funding; BMS: Research Funding; SeaGen: Research Funding; Teva: Research Funding; Genmab: Honoraria, Research Funding; Beigene: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Morphosys/Incyte: Consultancy, Honoraria; ADCT: Consultancy, Honoraria; Acrotech: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Cellectar: Consultancy, Honoraria; Compliment: Consultancy, Current holder of stock options in a privately-held company, Honoraria; Epizyme: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; Caribou: Consultancy, Honoraria; Fresenius-Kabi: Consultancy, Honoraria; Scitek: Consultancy, Honoraria; Sana: Consultancy, Honoraria. Ujjani:Abbvie, Astrazeneca, Beigene, Genentech, Jansen, Lilly, Pharmacyclics: Honoraria; AbbVie, Astrazeneca, Lilly, PCYC: Research Funding. Shadman:Morphosys/Incyte, Beigene, Genmab, AstraZeneca, Genentech, Abbvie: Consultancy, Research Funding; Vincerx, Janssen: Research Funding; Merck, Nurix, Fate Therapeutics, Eli Lilly, Kite Pharma, Bristol Myers Squibb: Consultancy; Koi Biotherapeutics: Current holder of stock options in a privately-held company; Bristol Myers Squibb (spouse): Current Employment.