LONG TERM DATA FOR HCL

Results from the largest report ever on young hairy cell leukemia (HCL) patients treated with standard chemotherapy — cladribine — are a mixed bag.

On the one hand, a majority of the 83 patients, all of whom were younger than 40 years at diagnosis and were treated at the Scripps Clinic in La Jolla, California, had a complete response to therapy. And, to the relief of the investigators, there was no significant increase in second cancers (compared with what was expected in age-matched normal subjects). The median follow-up was 251 months, or about 20 years.

On the other hand, the median response to cladribine in these relatively young HCL patients was only 57 months.

This does not compare favorably with the 98-month average found in a previous study of a Scripps population without age restrictions (J Clin Oncol. 2003;21:891-896). Furthermore, more young HCL patients in the current study relapsed after their first course of cladribine than in the 2003 study (58% vs 37%).

The new report was published in the January 9 edition of Blood.

The investigators, led by Joshua Rosenberg, MD, a fellow in oncology and hematology at Scripps, accent the positive in their conclusion. "Single courses of cladribine induce high rates of complete and durable responses in the majority of young HCL patients and are therefore recommended for HCL patients regardless of age," they write.

At the same time, they hope that "further investigations" into the biology of young HCL patients will yield insights that could result in "more efficacious" combination therapy.

The finding of no significant increase in risk for secondary primary malignancies was heartening to one expert.

"We are so encouraged [by the finding]," Martin Tallman, MD, chief of the leukemia service at the Memorial-Sloan Kettering Cancer Center in New York City, told Medscape Medical News in an email. Dr. Tallman was not involved in the research.

In the previous study of the Scripps population, 22% of the 379 HCL patients of all ages developed secondary primary malignancies. Dr. Rosenberg and colleagues found that the rate in their cohort of young HCL patients was only 9%.

"This is reassuring given the young age of these HCL patients and the initial concerns that cladribine-induced immunosuppression might be associated with the late development of second primary malignancies," the investigators write. HCL patients are typically diagnosed in their 60s, they point out.

Overall Survival Comparable to Another Cohort

HCL is an uncommon chronic B-cell lymphoproliferative disorder that is indolent but incurable. It is characterized by circulating B-cells with cytoplasmic projections, pancytopenia, splenomegaly, and recurrent infections, Dr. Rosenberg and colleagues report.

Researchers at the Scripps Clinic first reported the promising activity of cladribine in HCL patients in 1990. Since then, both cladribine and another nucleoside analog — pentostatin — have been found to induce long-lasting complete remissions in the majority of HCL patients.

Dr. Rosenberg's team examined data from as far back as 1986. Patients only received cladribine for an absolute neutrophil count below 1.0 × 10^(9)/L, a hemoglobin concentration below 10 g/dL, a platelet count below 100 × 10^(9)/L, and/or symptomatic splenomegaly.

"We use very similar parameters" at Memorial Sloan-Kettering, and cladribine is also the first-line treatment of choice, said Dr. Tallman. However, he explained that they use a hemoglobin concentration of 11 g/dL or less.

Dr. Rosenberg's team defined a complete response as the disappearance of all evidence of disease. In their cohort, cladribine was given as a 7-day continuous intravenous infusion at a dose of 0.1 mg/kg per day.

Of 83 evaluable patients, 73 (88%) achieved an initial complete response and 10 (12%) achieved a partial response. Forty-eight patients (58%) relapsed; the median time to first relapse for all responders was 54 months.

Eight patients developed 11 second primary malignancies, with an excess frequency of 1.60 (95% confidence interval [CI], 0.80 - 2.89). Thirteen (15%) patients died, and the mortality ratio compared with age-matched normal subjects was 1.85 (95% CI, 1.07 - 3.18).

Although 83 patients were evaluable in this study, the cohort consisted of 88 patients. The median overall survival for all 88 patients was 231 months from the time of first cladribine treatment, and there was 80% survival at 20 years.

This is comparable to the overall survival rate of 87% found at 12 years in an all-age cohort of HCL patients at Northwestern University by a team led by Dr. Tallman, before he transferred to Memorial Sloan-Kettering (Blood. 2005;106:241-246).

The authors and Dr. Tallman have disclosed no relevant financial relationships.

Blood. 2014;123:177-183. Abstract