Ibrutinib Shows Continued Activity in Relapsed, Variant-Type Hairy Cell Leukemia

Partner | Cancer Centers | <b>The Ohio State University</b>

Ibrutinib demonstrated encouraging clinical responses in patients with variant-type, high-risk hairy cell leukemia.

Ibrutinib (Imbruvica) demonstrated encouraging clinical responses in patients with variant-type, high-risk hairy cell leukemia (HCL), according to phase 2 findings of a multicenter trial (NCT01841723) that were published in Blood.1

In the study of 37 patients with classic (n = 28) or variant (n = 9) HCL, results showed that the 32-week objective response rate (ORR) was 24%; at 48 weeks, the ORR was 36%. The best overall response was 54%. 

“There is a critical unmet need for therapy options in this subset of patients to achieve long-term cancer control,” said principal investigator Kerry Rogers, MD, who is a hematologist/scientist at the Ohio State University Comprehensive Cancer Center—James, and an assistant professor at Ohio State College of Medicine.2 “Our study shows that ibrutinib is a safe, effective, and well-tolerated option for patients with relapsed or variant forms of hairy cell leukemia. It is a very important discovery for patients facing this diagnosis.”

HCL is diagnosed in 600 to 800 people each year in the United States. While the disease is typically associated with a good prognosis, there are prognostic indicators of poor outcomes. These patients do not benefit from or are intolerant of FDA-approved regimens.

For the phase 2 study, researchers wanted to determine whether the BTK inhibitor could be an effective agent for the subset of patients with the variant subtype who are unfit to receive standard regimens.

In the phase 2 trial, which began in 2013, 37 patients with classic or variant high-risk HCL were treated with ibrutinib in 28-day cycles. All patients had received prior treatment or were likely ineligible for standard therapies, such as cladribine and pentostatin.

The primary end point was 32-week ORR—which included both complete responses and partial responses—, as well as 48-week response and best response during treatment. Secondary end points were characterization of toxicity, progression-free survival (PFS), and overall survival (OS).

The first 13 patients on study received oral ibrutinib at 420 mg once daily, while the remaining patients were treated with the BTK inhibitor at 840 mg due to low responses in the initial group. However, after 32-week responses were recorded at the 420-mg dose, the trial protocol was amended to administer ibrutinib at 420 mg to newly enrolled patients because of toxicity-related concerns, and those on the 840-mg dose could be reduced to the 420-mg dose. Treatment was given until disease progression or unacceptable toxicities.

Prior findings, presented in October 2019, and from a smaller group of patients, showed that the ORR in this patient population was 50%, and the 3-year progression-free survival (PFS) rate was nearly 75%.

At a median follow-up of 3.5 years (range, 0-5.9 years), the 3-year PFS and OS rates was 73% and 85%, respectively.

Regarding safety, the most frequent adverse events (AEs) were diarrhea (59%), fatigue (54%), myalgia (54%), and nausea (51%). Hematologic AEs were anemia (43%), thrombocytopenia (41%), and neutropenia (35%).

The phase 2 study is now closed to patient accrual.

“Even though hairy cell leukemia is a disease with a generally good prognosis, there is a small group of patients for whom current therapies are inadequate for cancer control,” Rogers concluded. “This is an effective, well-tolerated new treatment option for patients impacted by the highest-risk forms of hairy cell leukemia. It’s a very exciting development that could transform survivorship for this subset of patients from months and years, to years and decades.”


  1. Rogers KA, Andritsos LA, Wei L, et al. Phase 2 study of ibrutinib in classic and variant hairy cell leukemia. Blood. 2021;137(25):3473-3483. doi:10.1182/blood.2020009688
  2. Study: Ibrutinib effective treatment for difficult to treat forms of hairy cell leukemia. News release. Ohio State University Comprehensive Cancer Center. July 21, 2021. Accessed August 20, 2021. https://bit.ly/3sz1Hr6