CLARITY: Ibrutinib Plus Venetoclax in Relapsed or Refractory Chronic Lymphocytic Leukemia


Key Points

  • MRD negativity was achieved in the peripheral blood in 53% of patients and in the bone marrow of 36%.
  • Response was observed in 89% of patients, with 51% achieving complete remission.

In the phase II CLARITY trial reported in the Journal of Clinical Oncology, Hillmen et al found that the combination of ibrutinib and venetoclax resulted in high rates of minimal residual disease eradication in patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

In the multicenter study, 53 evaluable patients enrolled between May 2016 and November 2017 received ibrutinib at 420 mg daily plus venetoclax started on day 1 of week 9 and given in a weekly ramp-up from a starting dose of 20 mg/d to 50 mg/d, 100 mg/d, 200 mg/d, and to the maximum dose of 400 mg/d. The primary endpoint was eradication of minimal residual disease, defined as < 1 CLL cell/10,000 leukocytes (MRD4), after 12 months of combined therapy.

Minimal Residual Disease Negativity

After 12 months of ibrutinib plus venetoclax (14 months of treatment), minimal residual disease negativity was achieved in the peripheral blood in 28 patients (53%) and in the bone marrow in 19 (36%). Overall, response was observed in 47 patients (89%), with 27 (51%) achieving complete remission.

At the time of data freeze, two patients had stopped taking ibrutinib plus venetoclax after confirmation of minimal residual disease–negative remission at month 14; at last observation, neither had experienced relapse, and both remained below MRD4 in peripheral blood and bone marrow. The remaining patients have continued therapy, including minimal residual disease–negative patients with residual lymphadenopathy. After a median follow-up of 21.1 months, disease progression had occurred in one patient, and all patients remained alive.

Adverse Events

Diarrhea was the most common adverse event of any grade. The most common grade 3 or 4 adverse events were decreased neutrophil count (63%), decreased platelet count (26%), lung infection (9%), and hypertension (9%). Overall, grade 3 or 4 infections occurred in 17% of patients.

A total of 34 serious adverse events were reported, with all resolving with appropriate management and all patients remaining in the study after resolution. Biochemical tumor-lysis syndrome was observed in one patient.

The investigators concluded, “The combination of ibrutinib plus venetoclax was well tolerated in patients with relapsed or refractory CLL. There was a high rate of [minimal residual disease] eradication that led to the cessation of therapy in some patients. The progression-free and overall survival rates are encouraging for relapsed and refractory CLL.”

Peter Hillmen, MBChB, PhD, of St James’s University Hospital, Leeds, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Bloodwise under the Trials Acceleration Programme, National Institute for Health Research Leeds Clinical Research Facility, Janssen-Cilag, and AbbVie. For full disclosures of the study authors, visit

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