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1660 Acalabrutinib in Patients with Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia Subjected to Allogeneic Hematopoietic Stem Cell Transplantation. a Phase 2 Study By the Polish Lymphoma Research Group

Program: Oral and Poster Abstracts
Session: 623. Mantle Cell, Follicular, Waldenstrom’s, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Lymphomas, Therapy sequence, Indolent lymphoma, Diseases, Treatment Considerations, Biological therapies, Lymphoid Malignancies, Transplantation (Allogeneic and Autologous)
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Sebastian Giebel, MD, PhD1*, Anna Czyz2*, Iwona Hus, MD3*, Lidia Gil, MD, PhD4, Krzysztof Giannopoulos, MD, PhD5*, Joanna Romejko-Jarosinska6*, Maciej Majcherek7*, Agnieszka Szeremet8*, Anna Wache9*, Paulina Kwasnik10*, Wlodzimierz Mendrek11* and Wojciech Jurczak, MD, PhD12

1Department of Bone Marrow Transplantation and Onco-Hematology, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland
2Deaprtment of Hematology, Medical University of Wroclaw, Wroclaw, Poland
3ul. Wołoska 137, The National Institute of Medicine of the Ministry of Interior and Administration, Warszawa, Poland
4Department of Hematology and Bone Marrow Transplantation, Poznan University of Medical Sciences, Poznan, Poland
5Department of Experimental Hematooncology, Medical University of Lublin, Lublin, Poland
6Maria Sklodowska-Curie Institute - Oncology Centre, Warsaw, Poland
7Medical University of Wroclaw, Wroclaw, Poland
8Wroclaw Medical University, Wroclaw, Poland
9Poznan University of Medical Sciences, Poznan, Poland
10Experimental Hematooncology Department, Medical University of Lublin, Lublin, Poland
11Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Gliwice, Poland
12Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Malopolskie, Poland

Background

Allogeneic hematopoietic cell transplantation (allo-HCT) Is a potentially curative option for patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL). The aim of this clinical trial was to evaluate safety and efficacy of acalabrutinib used to reduce tumor burden prior to allo-HCT and as a maintenance after transplantation in order to prevent relapse.

Methods

This was a phase 2, prospective, open label, multicenter study conducted by the Polish Lymphoma Research Group (clinicaltrials.gov: NCT04716075). Patients with R/R MCL and CLL, intended for allo-HCT were treated with acalabrutinib 100 mg BID for 3-6 months. Those achieving complete or partial response (CR, PR) and having appropriate donor were referred for allo-HCT. Acalabrutinib was restarted 30-90 days after allo-HCT and administered for subsequent 9 months. Remaining patients continued acalabrutinib until progression or unacceptable toxicity.

Results

Twenty-nine patients with MCL (n=28) and CLL (n=1) were included. For the purpose of this report the efficacy analysis was restricted to subjects with MCL. Median age was 61 (43-68) years. Median number of preceding lines of therapy was 1 (1-5), including autologous HCT in 11 cases. Twelve patients (43%) were refractory to last line of treatment. ECOG performance score was 1 (n=14) or 2 (n=14).

Sixteen patients (57%) responded to initial acalabrutinib treatment, including CR in 14 cases (50%) and PR in 2 cases (7%). Six patients (23%) achieved CR with negative status of minimal residual disease. Fifteen subjects (54%) underwent allo-HCT, from either matched sibling (n=3), unrelated (n=10) or haploidentical (n=2) donor.

With the median follow-up of 24 months, the probabilities of overall and progression-free survival (PFS) at 2 years were 60% (95%CI, 40-79) and 41.5% (23-60), respectively. Cumulative incidence of relapse and non-relapse mortality was 36% (18-55) and 22% (6-38), respectively. PFS rate for patients treated with allo-HCT was 67% (44-92) at 18 months. No events (progression or death in remission) were observed after 12 months.

The grade ≥3 adverse events were observed in 23 subjects, including neutropenia (n=10), anemia (n=3), thrombocytopenia (n=2), infections (n=6), gastrointestinal disorders (n=4) and neurological events (n=3). Five patients died of treatment-related complications, most frequently due to infections (n=4), including 2 cases of COVID-19 (the study was conducted during SARS-Cov-2 pandemia). Among allo-HCT recipients there were no cases of grade 3 or 4 acute graft-versus-host disease (GVHD). One patient experienced severe chronic GVHD.

Conclusions

Acalabrutinib generates high response rates in patients with R/R MCL. It may serve as a “bridge” to allo-HCT and maintenance after transplantation, offering a chance of cure for selected patients having available donor. Infections are the most frequent life-threating complications.

Disclosures: Giebel: Astra Zeneca: Honoraria, Speakers Bureau; Kite/Gilead: Consultancy, Honoraria, Speakers Bureau; Sobi: Consultancy, Honoraria, Other: Travel funding, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Abbvie: Consultancy, Honoraria, Speakers Bureau; Beigene: Honoraria, Speakers Bureau. Gil: Gilead, Abbvie, Roche, Novartis, Pfizer, Servier, Janssen, BMS, Takeda: Consultancy, Speakers Bureau; BMS, Gilead, Abbvie: Consultancy, Honoraria. Giannopoulos: Pfizer, TG Therapeutics, Abbvie, Amgen, Astra-Zeneca, Bei-Gene, Janssen, Sanofi-Genzyme, Novartis, Takeda, Roche, GSK, Gilead: Honoraria; Sandoz, Pfizer, TG Therapeutics, Abbvie, Amgen, Astra-Zeneca, Bei-Gene, Janssen, Sanofi-Genzyme, Novartis, Takeda, Roche, GSK, Gilead: Research Funding. Romejko-Jarosinska: Astra Zeneca: Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Sanofi: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau. Mendrek: Gilead: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Jurczak: Regeneron: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Merck: Research Funding; Lilly: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; MSD: Research Funding; Janssen Cilag: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding.

*signifies non-member of ASH