Dr Niemann on Long-Term PFS and Safety Outcomes With Ibrutinib Plus Ventoclax in CLL

“We already knew that PFS was improved with the ibrutinib combination. The question now was: Would this improvement be sustainable for a longer period of follow up? That's what we found in the longer-term follow-up data. [Moreover], the toxicity-free PFS was significantly improved by more than 20 months with ibrutinib and venetoclax vs chlorambucil and obinutuzumab, despite the longer length of treatment.”

Carsten Niemann, MD, PhD, chief physician, head, Laboratory at the Rigshospitalet Copenhagen University Hospital, discusses long-term follow-up data with fixed-duration ibrutinib (Imbruvica) plus venetoclax (Venclexta) in elderly or comorbid patients with previously untreated chronic lymphocytic leukemia (CLL) from the phase 3 GLOW trial (NCT03462719). These findings were presented at the 

The phase 3 GLOW study compared the safety and efficacy of a fixed-duration regimen of ibrutinib plus venetoclax with chlorambucil plus obinutuzumab (Gazyva) in patients with CLL. At a median follow-up of 64 months, the combination of ibrutinib and venetoclax significantly improved progression-free survival (PFS), reducing the risk of progression or death by 73% compared with the chlorambucil/obinutuzumab regimen (HR, 0.27; 95% CI, 0.18-0.39; 

 < .0001). The 60-month PFS rates were 59.9% for ibrutinib plus venetoclax and 17.8% for chlorambucil plus obinutuzumab. The longer-term data confirmed the durability of the PFS benefit previously observed with the ibrutinib and venetoclax combination, Niemann states.

Additionally, the study assessed the toxicity profile of the ibrutinib and venetoclax regimen, particularly grade 3 or higher adverse effects, given the longer treatment duration compared with the control arm, Niemann reports. Overall, patients spent less time in the grade 3/4 treatment-emergent AE and progressive disease health state with the ibrutinib combination vs the control regimen. Further analysis showed that the PFS time free from grade 3/4 toxicity or relapse was extended by 21.4 months in the ibrutinib and venetoclax arm (51.6 months) relative to the chlorambucil and obinutuzumab arm (30.2 months; nominal 

 = .0052), Niemann reports. highlighting the combination’s favorable balance of clinical benefit and manageable toxicity despite the extended treatment duration, he concludes.

Videos

Carsten Niemann, MD, PhD, discusses long-term follow-up data from the phase 3 GLOW trial evaluating fixed-duration ibrutinib plus venetoclax in CLL.

Dr Niemann on the Investigation of Ibrutinib Plus Ventoclax in CLL

Implications of ESMO Guidelines for IGHV-Mutated vs Unmutated CLL 

Video content above is prompted by the following:

Briefly review recent ESMO guideline updates for the frontline management of patients with IGHV-unmutated or mutated and no TP53 mutation and discuss associated implications.

A panel of medical experts provides an overview of recent ESMO guideline updates on frontline management for patients with IGHV-mutated or unmutated chronic lymphocytic leukemia (CLL) without TP53 mutations, highlighting key clinical implications.

Implications of ESMO Guidelines for IGHV-Mutated vs Unmutated CLL

How does your treatment approach differ for IGHV-mutated vs unmutated CLL?

A panel of medical experts continues their discussion surrounding an array of treatment options for CLL.

Tailoring Treatment Approaches for Fit vs Unfit CLL Patients 

Recent Guideline Updates in the Frontline Management of CLL

Provide a brief review of the evolving treatment landscape for newly diagnosed CLL.

Available therapy options (time-limited vs continuous).

Preference for targeted therapy approaches over conventional chemotherapy.

Key challenges and unmet needs in the 1L setting.

Dr Niemann provides an overview of the evolving treatment landscape of CLL.

Carsten Niemann, MD, PhD, a chief physician, and head of Laboratory at the Rigshospitalet Copenhagen University Hospital, discusses notable data on patient survival outcomes, as well as the impact of minimal residual disease (MRD) in the peripheral blood from the phase 3 GLOW trial (NCT03462719) in patients with chronic lymphocytic leukemia (CLL).

The main goal of the phase 3 GLOW study was to examine progression-free survival (PFS) in patients treated with a fixed duration of ibrutinib (Imbruvica) plus venetoclax (Venclexta) vs chlorambucil and obinutuzumab (Gazyva) in the first-line setting of CLL.

When an overall survival benefit was seen in this patient population, it came as a surprise due to the fact that there are many viable next-line treatment options for patients, Niemann begins. Moreover, a majority of patients who were receiving treatment with chlorambucil and obinutuzumab received a BTK or BCL-2 inhibitor in subsequent lines of therapy, Niemann explains. These data indicate that lower survival outcomes should not be attributed to a lack of access to next-line treatment, but rather should be attributed to a lack of effective upfront therapy options, Niemann explains.

Furthermore, it is important to look at the differences seen in terms of targeting various areas of an individual patient’s CLL, such as the bone marrow, blood, and lymph nodes. Clinicians observed lymph node responses in patients with detectable vs undetectable MRD. Specifically, it was found that patients who presented with detectable MRD in the peripheral blood had sustained lymph node responses, Niemann adds.

Treatment for patients with BTK and BCL-2 inhibitor combination regimens, this may correlate with undetectable MRD levels and superior PFS.

Carsten Niemann, MD, PhD, discusses notable data on patient survival outcomes, as well as the impact of minimal residual disease in the peripheral blood from the phase 3 GLOW trial in patients with chronic lymphocytic leukemia.

Dr. Niemann on Notable Findings from the GLOW Trial in CLL

Carsten Niemann, MD, PhD, chief physician, head of Laboratory, Rigshospitalet Copenhagen University Hospital, discusses ibrutinib (Imbruvica) plus venetoclax (Venclexta) vs chlorambucil and obinutuzumab (Gazyva) in mutated chronic lymphocytic leukemia (CLL).

The phase 3 GLOW study (NCT03462719) examined progression-free survival (PFS) with ibrutinib plus venetoclax vs chlorambucil and obinutuzumab in the first-line setting.

With longer follow-up, investigators found that patients with unmutated 

 who have detectable minimal residual disease (MRD) have shorter PFS, Niemann says. Notably, 

unmuted patients achieving undetectable MRD levels after treatment have a good PFS rate above 90% at 3.5 years of follow-up.

 mutations have favorable PFS regardless of MRD status, Niemann concludes.

Carsten Niemann, MD, PhD, discusses ibrutinib plus venetoclax vs chlorambucil and obinutuzumab in mutated chronic lymphocytic leukemia.

Carsten Niemann, MD, PhD

Articles

Dr Niemann on the Investigation of Ibrutinib Plus Ventoclax in CLL

Implications of ESMO Guidelines for IGHV-Mutated vs Unmutated CLL

Tailoring Treatment Approaches for Fit vs Unfit CLL Patients

Recent Guideline Updates in the Frontline Management of CLL

Dr. Niemann on Notable Findings from the GLOW Trial in CLL

Dr. Niemann on Ibrutinib Plus Venetoclax Vs Chlorambucil and Obinutuzumab in Mutated CLL