ASH 2021 – Jennifer A. Woyach
Jennifer A. Woyach explains which factors need to be considered when choosing the frontline regimen for patients with early-stage CLL, how resistance to BTK inhibition can be tackled in later lines, if chemoimmunotherapy still has a role in the treatment of CLL and highlights the most interesting findings on the management of treatment-naïve CLL patients.
Here is the full ASH 2021 report.
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Promising novel approaches in various B-cell malignancies
For more than 20 years, the R-CHOP regimen consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone has been the standard of care in the first-line treatment of diffuse large B-cell lymphoma (DLBCL). However, as only 60-70 % of patients achieve cure, there is a need to improve on these results. The antibody-drug conjugate polatuzumab vedotin that targets CD79b has already shown activity in combination with rituximab or obinutuzumab plus cyclophosphamide, doxorubicin, and prednisone (CHP) in a phase II study conducted in the first-line setting of DLBCL.
Phase II data on novel BTK inhibitors for patients with Waldenström’s macroglobulinemia
Second-generation BTK inhibitors such as orelabrutinib and tirabrutinib are currently being evaluated in the treatment of Waldenström’s macroglobulinemia (WM). Orelabrutinib is a BTK inhibitor with excellent target selectivity and almost 100 % BTK occupancy. At ASH 2021, Zhou et al. reported the results for 47 patients with relapsed/refractory WM who received orelabrutinib 150 mg/d in the single-arm, multicenter, open-label, phase II ICP-CL-00105 study.
Marginal zone lymphoma: PI3Kδ inhibition and beyond
First-line treatment for patients with marginal zone lymphoma (MZL) typically includes anti-CD20-based regimens that generally evoke high response rates. However, in most cases, serial relapses eventually require several lines of therapy. The phase II CITADEL-204 trial evaluated the highly selective, next-generation PI3Kδ inhibitor parsaclisib in patients with relapsed/refractory MZL with or without prior exposure to ibrutinib.
Mantle cell lymphoma: refining clinical outcomes beyond the current boundaries
Targeted therapies including BTK inhibitors are used in the second- and later-line treatment of patients with mantle cell lymphoma (MCL), although intolerance and treatment failure are common, with poor survival outcomes in the relapsed and refractory setting. This highlights the need for novel agents such as the potent and highly selective next-generation PI3Kδ inhibitor parsaclisib.
Management of patients with relapsed/refractory CLL: what is new?
The optimal novel-agent approach for patients with chronic lymphocytic leukemia (CLL) is subject to research. Targeted therapies have become the undisputed standard of care in both relapsing/refractory and treatment-naïve settings. The choice of regimen remains, however, disputable. Continuous BTK inhibition confers the risk of cumulative toxicity and acquired resistance, while time-limited combination therapies may result in relatively high adverse event (AE) rates and lead to overtreatment of patients with favorable risk.
Determining first-line CLL/SLL treatment strategies with optimized efficacy and safety
The international, randomized, phase III GAIA/CLL13 study was conducted to identify the optimal time-limited first-line treatment regimen for fit patients with chronic lymphocytic leukemia (CLL). Standard chemoimmunotherapy (CIT) consisting of fludarabine, cyclophosphamide and rituximab (FCR; patients ≤ 65 years) or bendamustin plus rituximab (BR; patients > 65 years) was compared to venetoclax-based, limited-duration strategies.
