Published on August 28, 2020
CLL Patients Achieve Complete Remission With New Combination Therapy
A three-drug combination therapy has shown to be effective in achieving complete remission in more than half of previously untreated patients with high-risk chronic lymphocytic leukemia (CLL).
The regimen of ibrutinib (Imbruvica), venetoclax (Venclexta) and obinutuzumab (Gazyva) — all targeted drugs for the blood cancer — increased CLL remission in 58.5% of the patients in phase II of the CLL2-GIVe clinical trial, with another 34.2% showing a partial response. Additionally, 80.4% showed minimal residual disease (MRD) in their blood after 15 cycles of treatment or a median follow-up of 18.6 months.
"The GIVe regimen is promising first-line therapy for patients with high-risk CLL," said study author Dr. Henriette Huber of University Hospital Ulm, Germany, in a presentation at the annual Congress of the European Hematology Association held virtually in June.
All three drugs are already used in CLL treatment, either alone or with other drugs. Each targets a different cancer-driving protein. Ibrutinib inhibits Bruton’s tyrosine kinase (BTK); venetoclax is a B-cell lymphoma 2 (BCL-2) inhibitor; and obinutuzumab is an antibody against CD20, which is found on B cells, a type of white blood cell that produces antibodies.
Remission in CLL Through Combination Therapies
The CLL landscape has changed dramatically over the years, said Dr. Nitin Jain, an associate professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston, Texas, in a recent interview with Patient Power Co-Founder Andrew Schorr.
Fludarabine cyclophosphamide rituximab (FCR) used to be the standard of care — and still is for select patients, he said. (Schorr, who has CLL, participated in the phase II trial for FCR, and had a 17-year remission after six months on the therapy.) But these days patients are receiving newer, targeted therapies. Combination therapies are also proving to be more effective treatment options than single agents.
“…One of the things which our group and other investigators in the field have been working on is trying to combine these drugs together to find maybe an optimal regimen, which can be given not for lifelong, but for a well-defined period of time,” Dr. Jain told Schorr. “And then to maximize the chance that the patients get deep remission and then to be able to stop therapy.”
CLL Clinical Trials Lead to FDA Approvals
In May 2019, the FDA approved the combination of venetoclax and obinutuzumab for the frontline cancer treatment of patients with CLL. The approval was based on findings from the phase III CLL14 trial, in which the combination led to a 65% reduction in the risk of disease progression or death compared with obinutuzumab plus the chemo drug chlorambucil.
Five months prior, the FDA approved the combination of ibrutinib and obinutuzumab as a first-line treatment for patients with CLL based on data from the phase III iLLUMINATE (PCYC-1130) trial. Ibrutinib/obinutuzumab led to a 77% reduction in the risk of disease progression or death versus chlorambucil/obinutuzumab.
The GIVe study of 41 patients (24 of whom were men) included people from age 35 to 85 with a median age of 62. Twenty-six patients had del(17p), 39 had TP53 mutations, and 32 patients had an unmutated IGHV gene. All patients received treatment with the combination for six months.
In terms of safety, the combination was well tolerated. Serious or severe side effects included low neutrophil counts (43.9%), infections (19.5%), low platelet counts (14.6%) and infusion-related reactions (7.3%).
CLL Treatments Continue to Improve
“All these drugs, you can already do great, but can you make them even better?” Dr. Jain said. “Can you make the duration of drugs to be given shorter, which I think would help everyone in terms of time-limited therapy? So, I think that's a big excitement in the field and I see a lot of researchers, myself, our group here, and many other groups are working in developing what is called time-limited therapy. So, give the drugs for one to two years and then be able to stop the drugs. Then you enter what is called a treatment-free remission period. And then hopefully that will last for years and years to come.”
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- Huber H, Edenhofer S, Tresckow JV, et al. CLL2-GIVE, a prospective, open-label, multicenter phase-II trial of obinutuzumab (GA101, G), ibrutinib (I), plus venetoclax (VE) in untreated patients with CLL with 17p deletion / TP53 mutation. Presented at: 2020 European Hematology Association Congress; July 11 to 21, 2020; Virtual. Abstract S157.
- U.S. FDA Approves IMBRUVICA® (ibrutinib) Plus Obinutuzumab as First Non-Chemotherapy Combination Regimen for Treatment-Naïve Patients with Chronic Lymphocytic Leukemia
- FDA Approves Chemotherapy-Free Regimen, Venetoclax Plus Obinutuzumab, as First-Line Treatment for CLL/SLL
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