After one year of treatment with ibrutinib plus venetoclax, relapsed or refractory chronic lymphocytic leukemia (CLL) patients on the single-arm, phase II CLARITY trial had high rates of measurable residual disease (MRD) negativity, according to trial results recently published in the Journal of Clinical Oncology.
The CLARITY study enrolled 54 patients with relapsed or refractory CLL who received ibrutinib in combination with venetoclax. The primary endpoint for the trial was MRD negativity after 12 months of treatment. MRD negativity was defined as having less than one CLL cell in 10,000 leukocytes.
Most study patients were male (69%), and patients received a median of one prior therapy (range: 1 to 6 therapies). The majority of patients (83%) previously received either fludarabine, cyclophosphamide, and rituximab or bendamustine and rituximab. Twenty percent previously received a treatment regimen that included idelalisib. In addition, 19% of patients had mutated IGVH genes, 22% had deletion 17p, and 20% had deletion 11q, but not deletion 17p.
The idea was to “synergize” the mechanisms of action for ibrutinib and venetoclax and try to achieve eradication of MRD, said Sravanti Teegavarapu, MD, assistant professor of hematology and oncology at Baylor College of Medicine in Houston, during an interview with Cancer Network. Teegavarapu was not involved in the CLARITY trial.
“MRD in CLL is mainly a good marker for trying to look at long-term remissions, as we know that people who are MRD-negative tend to have a better outcome than those who are MRD-positive,” she explained.
The most common adverse events were diarrhea and decreased neutrophil count. One patient had grade 3 biochemical tumor lysis syndrome, and there were 34 events of grade 3 or 4 neutropenia and 9 events of grade 3 or 4 infections.
After 12 months of combination therapy, 28 (53%) patients achieved MRD negativity in the peripheral blood and 19 (36%) achieved MRD negativity in the marrow. A total of 47 patients (89%) achieved a response, of which 27 (51%) were complete responses. MRD negativity was also assessed after 6 months and 24 months of combination therapy.
Teegavarapu commented that the MRD negativity rate achieved at 12 months was “pretty impressive,” compared to what has been seen thus far, and the overall response rate was “quite high.”
By assessing MRD negativity at time points, Teegavarapu explained, the trial investigators were able to draw a timeline and have these patients stop treatment after they achieved MRD negativity. “Most of these patients who are [on] monotherapies tend to continue these treatments almost indefinitely.”
Teegavarapu said the “big question” that always arises is whether the eradication of CLL cells is permanent. “[The study] definitely needs a longer follow up,” she said. Currently, the phase 3 FLAIR trial is ongoing and aims to compare four treatment groups in treatment-naïve CLL, one of which is ibrutinib plus venetoclax.
“Hopefully that [study] will shed a little bit more light and maybe have a longer follow-up as to how these patients are doing,” Teegavarapu added.