acalabrutinib + alloSCT

Acalabrutinib combined with allogeneic stem cell transplantation (alloSCT) represents a treatment approach being investigated for patients with refractory/relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) with poor prognostic factors. This combination therapy strategy involves using acalabrutinib both before and after transplantation to improve outcomes. ### Treatment Approach In this therapeutic strategy, acalabrutinib is administered: - **Before transplantation**: To reduce tumor burden prior to the alloSCT procedure - **After transplantation**: To augment disease control following the procedure The approach is being studied in a phase II multicenter trial for patients with refractory/relapsed MCL and CLL with poor prognostic factors who undergo alloSCT with reduced intensity conditioning (RIC)[1]. ### Potential Benefits Researchers hypothesize that this combination approach may: - Improve the efficacy of alloSCT through serial minimal residual disease (MRD) evaluation - Potentially reduce the severity and incidence of chronic graft-versus-host disease (GvHD), as acalabrutinib is a BTK inhibitor similar to ibrutinib, which has shown this effect[1] - Significantly improve outcomes for poor prognosis MCL and CLL patients[1] ### Current Research The phase II multicenter trial plans to enroll 25 transplanted patients, with primary endpoints focusing on best response to therapy and safety issues. The trial will specifically assess treatment-emergent adverse events (TEAE) and serious adverse events (SAE) of acalabrutinib in patients after alloSCT, which has not been previously assessed[1]. ### Context in CLL Treatment AlloSCT has traditionally been considered the treatment of choice for high-risk CLL patients and the only potentially curative approach for the disease[2]. However, with the emergence of novel agents like BTK inhibitors (including acalabrutinib) and BCL2 inhibitors, the role of alloSCT in the treatment algorithm has become more complex[2]. For highest-risk CLL patients (those with TP53 deletion/mutation, chemoimmunotherapy refractory disease, or early relapse after FCR treatment), the current approach often involves induction with novel agents followed by consideration of alloSCT in suitable patients[2]. A combination therapy approach using acalabrutinib (a BTK inhibitor) before and after allogeneic hematopoietic stem cell transplantation (alloSCT) for patients with refractory/relapsed mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) with poor prognostic factors. Acalabrutinib is administered before alloSCT to reduce tumor burden and after transplant to augment disease control. This approach may also potentially reduce the severity and incidence of chronic graft-versus-host disease (GvHD).