Chronic Lymphocytic Leukemia

Prioty Islam, MD, MSc, discusses findings from the BRUIN trial, highlights the potential benefits of using noncovalent BTK inhibitors instead of or before covalent BTK inhibitors in patients with MCL or CLL, and previewed ongoing clinical trials investigating this class of agents in earlier treatment lines in these populations.

Treatment with fixed-duration ibrutinib plus venetoclax for patients with chronic lymphocytic leukemia in the first-line setting elicited durable responses and sustained progression-free survival outcomes regardless of high-risk genomic features.

Administration of glofitamab after pretreatment with obinutuzumab provided encouraging antitumor activity with high and durable complete response rates and a manageable safety profile in heavily pretreated patients with Richter syndrome.

Susan M. O’Brien, MD, discusses the use of pirtobrutinib for patients with hematologic malignancies who developed resistance to BTK inhibition.

The treatment landscape for PNH is rapidly evolving, and clinicians have more effective and convenient treatment options for patients that have helped control the disease and improve survival. T

Alexey Danilov, MD, PhD, presents an analysis of data from the Phase 1 TRANSCEND CLL 004 study investigating lisocabtagene maraleucel in patients with relapsed/refractory CLL or SLL.

Paolo Ghia, MD, PhD, reviews data from the ELEVATE-RR trial investigating acalabrutinib versus ibrutinib for the treatment of relapsed/refractory chronic lymphocytic leukemia (R/R CLL).

The choice of BTK inhibitor regimen for patients with chronic lymphocytic leukemia must be tailored to the patient, taking into consideration their preferences and comorbidities, as well as potential treatment-related adverse effects.

Key opinion leader Mazyar Shadman, MD, MPH, reviews data from a clinical trial studying zanubrutinib in the context of ibrutinib- and/or acalabrutinib-intolerant CLL/SLL.

The combination of venetoclax, atezolizumab, and obinutuzumab elicited responses and prolonged time progression, in patients with chronic lymphocytic leukemia with Richter transformation, according to data from the phase 2 MOLTO trial.

John M. Burke, MD, expands on the use of novel BTK inhibitor regimens in mantle cell lymphoma, treatment sequencing challenges and other unmet needs in diffuse-large B-cell lymphoma, the evolution of management strategies for myeloproliferative neoplasms, and the potential influence of new and emerging therapeutics in chronic lymphocytic leukemia.

Fixed-duration therapy with venetoclax plus obinutuzumab led to 60% reduction in the risk of progression or death compared with chlorambucil plus obinutuzumab, with benefit seen regardless of TP53 or IGHV mutation status, in previously untreated patients with chronic lymphocytic leukemia.

Zanubrutinib plus obinutuzumab and venetoclax demonstrated lasting responses characterized by sustained progression-free survival and undetectable minimal residual disease in peripheral blood and bone marrow in previously untreated patients with chronic lymphocytic leukemia or small lymphocytic lymphoma.

Extended follow-up from the phase 3 SEQUOIA trial demonstrated that zanubrutinib maintained a progression-free survival benefit compared with bendamustine plus rituximab in previously untreated patients with chronic lymphocytic leukemia or small lymphocytic lymphoma.

Patients with relapsed/refractory chronic lymphocytic leukemia treated with ibrutinib in the phase 3 RESONATE trial achieved a significantly longer median progression-free survival compared with those in the phase 3 ALPINE trial, as well as a higher yet nonsignificant 2-year PFS estimate vs those in the phase 3 ELEVATE-RR trial.

Luke J. Mountjoy, DO, discusses the implications of the SEQUOIA and the ALPINE trial, the importance of coming up with feasible and effective treatment options for patients with 17p deletions and TP53 mutations, and the investigation of liso-cel in patients with relapsed/refractory CLL.

Ibrutinib did not prolong survival vs placebo and is linked with increased susceptibility to bleeding in patients with asymptomatic early-stage chronic lymphocytic leukemia, suggesting that a watch-and-wait approach should continue as the standard for this population.

Treatment with fixed-duration venetoclax plus rituximab continued to show superior survival benefit vs bendamustine and rituximab in patients with relapsed/refractory chronic lymphocytic leukemia, according to 7-year follow up data from the phase 3 MURANO trial.

Acalabrutinib is safe in patients with chronic lymphocytic leukemia who are at least 80 years of age and/or frail.

Acalabrutinib and zanubrutinib demonstrated similar investigator-assessed progression-free survival in patients with relapsed/refractory chronic lymphocytic leukemia.

The combination of venetoclax and obinutuzumab with or without ibrutinib generated higher rates of undetectable minimal residual disease (MRD) and progression-free survival vs chemoimmunotherapy in fit patients with chronic lymphocytic leukemia.

Yiming Wu, PhD, discusses the rationale for studying splicing defects in patients with chronic lymphocytic leukemia without spliceosome mutations, shared key findings from this study, and emphasized how these findings support further research with METTL3 in chronic lymphocytic leukemia and other hematologic malignancies with RNA splicing dysregulation.

China’s National Medical Products Administration has approved 2 supplemental new drug applications of zanubrutinib for use in treatment-naïve adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma and Waldenström macroglobulinemia.

Yiming Wu, PhD, discusses a study identifying METTL3-mediated N6-methyladenosine modification as a key translational regulator of splicing factors, and how this mechanism contributes to the progression of chronic lymphocytic leukemia.

Canada Health has approved the fixed-duration, all-oral combination of ibrutinib and venetoclax for the frontline treatment of adult patients with chronic lymphocytic leukemia, including those with 17p deletion.

Closing out their discussion on novel treatment strategies in CLL, expert hematologist-oncologists address unmet needs and future directions in care.

An in-depth review of novel therapeutic targets making their way into clinical trials for patients with chronic lymphocytic leukemia.

Anthony Mato, MD, MSCE, discusses recent data on the emerging class of noncovalent BTK inhibitors in chronic lymphocytic leukemia and their potential advantage over currently approved covalent BTK inhibitors.

Following their discussion on novel therapeutic agents in chronic lymphocytic leukemia, panelists consider how these agents might be sequenced for optimal efficacy.

Expert perspectives on the novel use of ant-CD20 therapy as first-line or combination treatment in chronic lymphocytic leukemia.