Page 108 - Haematologica Vol. 110 - January 2025

ARTICLE - Pirtobrutinib in patients with prior intolerance to BTKi N.N. Shah et al.
demonstrated by a pirtobrutinib ORR of 76.9% and 81% for patients with CLL/SLL and MCL, respectively. Of note, for the 4 patients who discontinued prior nemtabrutinib for toxicity, 3 achieved a partial response to pirtobrutinib and one had stable disease. All 3 patients who achieved a partial response were still on treatment (17.2, 19.9, and 24.7 months) at the time of the data cutoff, and the one patient who had stable disease discontinued treatment after 19.8 months to start alternative therapy. For CLL specifically, this could delay switching to another class of drugs such as venetoclax-based treatment that often requires frequent initial visits and monitoring to reduce the risk of tumor lysis syndrome.22-25
This analysis of prior BTKi intolerant patients treated with pirtobrutinib has limitations. In particular, it was an explor- atory subgroup analysis from a single-arm study, and data for AE while on prior BTKi treatment, including the grade of the AE that led to discontinuation, were limited. We also cannot be entirely certain if discontinuations from combi- nation regimens were due to agents other than pirtobruti- nib. It is important to note, however, that the vast majority (110/127, 86.6%) of the patients in this study discontinued prior BTKi given as a monotherapy, and the most common combination therapy previously administered was a BTKi plus a CD20 monoclonal antibody (16/127, 12.6%), in which the CD20 monoclonal antibody was given for a fixed number of cycles, while treatment with BTKi also continued until disease progression or intolerance, mitigating the concern for an underestimate of pirtobrutinib-related toxicities. Furthermore, the number of patients who received prior treatment with acalabrutinib and zanubrutinib, which are now more commonly prescribed due to an improved AE profile, was low relative to patients who received prior treatment with ibrutinib.
In summary, pirtobrutinib monotherapy was safe and well-tolerated in the majority of patients with B-cell malig- nancies with documented intolerance to prior BTKi therapy. Most patients did not experience recurrence of the same AE or AE category that had led to discontinuation of the prior BTKi, and among those who did, none discontinued pirtobrutinib for this AE. Patients who discontinued prior BTKi due to intolerance had high response rates with pirto- brutinib, suggesting that pirtobrutinib may be an important consideration to extend the benefit of BTK inhibition among patients without progressive disease that are intolerant to a prior BTKi.
Disclosures
The following authors have received payments for grants/ contract, consulting fees, honoraria, and meetings: NNS - Loxo Oncology, Miltenyi Biomedicine, Genentech, Gilead-Kite, Novartis, Janssen, BMS-Juno, Seattle Genetics, Galapa- gos, BeiGene, Abbvie, Cargo; reports stock from Tundra Therapeutics. MW - Acerta Pharma, AstraZeneca, BeiGene, BioInvent, Celgene, Genmab, Genentech, Innocare, Jans-
sen, Juno Therapeutics, Kite Pharma, Lilly, Loxo Oncology, Molecular Templates, Oncternal, Pharmacyclics, Vincerx, AbbVie, ADC Therapeutics America, Amphista Therapeutics Limited, bE Biopharma, Bristol Myers Squibb, Deciphera, Merck, Miltenyi Biomedicine, Parexel, Pepromene Bio, Phar- macyclics, CAHON, Catamount Medical Education, Dava Oncology, MJH Life Sciences, MSC National Research Insti- tute of Oncolgy, NIH, Nurix, Physicians Education Resources (PER), Research to Practice, Scripps, Studio ER Congressi, South African Clinical Hematology Society, WebMD. LER - Adaptive Biotechnologies, AstraZeneca, Genentech, AbbVie, Pfizer, Aptose Biosciences, Dren Bio, Qilu Puget Sound Bio- therapeutic, Ascentage, BeiGene, Janssen, Loxo Oncology, Pharmacyclics, TG Therapeutics, DAVA, Curio, Medscape, PeerView, Abbott Laboratories. KP - AstraZeneca, Adaptive; received consulting fees from Abbvie, ADC, BeiGene, BMS, Caribou, Fate Therapeutics, Genentech/Roche, Janssen/ Pharmacyclics, Kite, Loxo Oncology, Merck, Morphosys, Sa- na, Xencor. JAW - National Cancer Institute, Leukemia and Lymphoma Society, CLL Global Society, Abbvie, AstraZeneca, BeiGene, Genentech, Janssen, Loxo Oncology, Merck, Ne- wave, Pharmacyclics, Gilead. WGW - GSK/Novartis, Abbvie, Genentech, Pharmacyclics LLC, AstraZeneca/Acerta Pharma, Gilead Sciences, Bristol Myers Squibb (Juno & Celgene), KITE Pharma, Oncternal Therapeutics, Inc., Cyclacel, Loxo Oncology, Janssen, Xencor, Janssen Biotech, Nurix Therapeu- tics, Numab Therapeutics, National Comprehensive Cancer Network (Chair, CLL) and NIH/NCI under award number P30 CA016672 and used MDACC Cancer Center Support Grant (CCSG) shared resources. CSU - Abbvie, AstraZeneca, Atara, BeiGene, Bristol Myers Squibb, ADC Therapeutics, Allogene, Genentech, Janssen, Epizyme, Pharmacyclics, Eli Lilly and Company, Clinical Care Options, Medscape, Onclive, Curio Sciences, ASCO, ASH, Atara. TAE - BeiGene, AstraZeneca, Loxo Oncology, Janssen, Lilly, Abbvie, Roche, KITE Gilead. PLZ - MSD, Eusapharma, Novartis, Celltrion, Gilead, Janssen-Ci- lag, BMS, Servier, AstraZeneca, Takeda, Roche, Kyowa Kirin, Incyte, BeiGene, Secura Bio, Sandoz, MSD, Kyowa Kirin, ADC Therap. AJA - Loxo Oncology, BeiGene, Incyte, ONO, Dr Reddy, Amgen, TG Therapeutics, ADC Therapeutics, Genentech, Eli Lilly and Company, Janssen, Epizyme, Seagen. PG - BMS, AbbVie, AstraZeneca, Janssen; BeiGene, Galapagos, Loxo Oncology, MSD, Roche. NL - AbbVie, Adaptive Biosciences, Allogene Therapeutics, AstraZeneca, BeiGene, Genentech, Janssen, Loxo Oncology, Pharmacyclics; received honoraria from Aptitude Health, BioAscend, Clinical Care Options, Curio, DAVA Oncology, OncLive, PER, Peerview, Targeted Oncology; Genmab, Eli Lilly, MingSight, Octapharma, Oncternal. MSH - AbbVie, Kite, ADC Therapeutics, BeiGene, Genentech, Astra- Zeneca, Pharmacuclics, Janssen, Novartis, TG Therapeutics. MRP - Institutional research funding. IF received grants or contracts (to institution) from AbbVie, Acerta Pharma, Agios, ArQule, AstraZeneca, BeiGene, Biopath, Bristol Myers Squibb, CALIBR, CALGB, Celgene, City of Hope National Medical Center, Constellation Pharmaceuticals, Curis, CTI Biophar-
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