Introduction: Hairy cell leukemia (HCL) is a chronic mature B-cell neoplasm with a very indolent clinical course and patients may survive for many decades. First-line treatment with purine analogues such as cladribine (Cld) is considered standard of care since it is very efficient and induces profound remissions. However, patients with HCL often relapse after purine analogues and repeated treatment may increase morbidity and mortality. Despite good clinical evidence of long term control of the disease by several mainly single center studies of patients treated with purine analogues, there is only one study analyzing mainly subcutaneous (sc) treated patients based on registry data. We therefore performed a pooled long-term follow-up analysis of our prospective multicenter studies treating patients with sc Cld focusing on survival, secondary malignancy and retreatment.

Materials and Methods: The SAKK included patients treated for HCL in 4 studies between 1993 and 2005. Three studies focused on first-line regimens with sc Cld, whereas the fourth protocol focused on the effect of Rituximab monotherapy in patients pretreated with Cld. Classical morphologic, immunohistochemistry and flow cytometry criteria were used as inclusion criteria and response was assessed by established criteria. Treatment algorithms in the 4 studies were as follows: 1) 5 days of Cld 0.14mg/kg sc followed by max 2 cycles of 7 days of Cld 0.1mg/kg sc in case of minor response or no response (SAKK 32/93); 2) Single shot of Cld 0.25mg/kg sc followed by a maximum of 2 cycles of 0.14mg/kg sc for 5 day in case of minor response, no response or relapse (SAKK 32/95); 3) 5 consecutive days of Cld 0.14mg/kg sc versus the same dose in 5 weekly applications (SAKK 32/98); 4) Rituximab 375 mg/m2iv weekly for 4 weeks in relapsed patients (SAKK 31/98). SAKK 32/93 included 63, SAKK 32/95 74 and SAKK 32/98 100 patients. Of the 26 patients registered in 31/98 20 were already in SAKK 32/93, 32/95 and 32/98. Therefore, we also included the treatment information and follow-up data of these 20 patients. All patients were subject to life-long follow-up within the clinical trials. Further information including secondary malignancies and retreatments were obtained by sending out questionnaires to the treating physicians of the study patients. Of the 237 patients 4 patients were in two of the studies and 10 patients have been excluded because of non-classical HCL phenotype. Therefore, a total of 223 patients were included in the analysis. Overall survival and follow-up time were assessed by Kaplan-Meier and reverse Kaplan-Meier method, respectively.

Results: The median age of patients at the time of diagnosis was 55 (range 21 to 96) years, 50 patients were female (22.4%) and 173 (77.6%) male. At the time of data analysis, the median follow-up time was 12.1 (95%-CI 10.0 to 14.0) years. A total of 129 (57.8%) patients had the last follow-up information more than two years prior to the data cut-off in May 2016, however, the available information of all patients was used for the sub-analyses including secondary malignancies or retreatment. By the cut-off date, 49 patients have died, 14 (28.6%) due to secondary malignancies and 7 (14.3%) due to HCL progression. Median overall survival from diagnosis was 31.6 (95%-CI 31.6 to 37.8) years. Retreatment was necessary in 53 (23.7%) patients after a mean of 6 (0.2 to 20.4) years and first retreatment was mainly Cld (64%), rituximab (19%) or Cld and rituximab (13%). 21 patients (9.4%) required more than one retreatment with a mean number of 1.57 (range 1 to 5) treatments. A total of 42 (18.8%) patients developed secondary malignancies with an average time to occurrence of 7.1 (range: 0.1 to 17.7) years. The majority of the secondary malignancies were of non-hematological origin (85.9%), most frequently skin cancer (31.0%), followed by prostate cancer (19.0%) and colorectal cancer (16.7%). Six patients (14.4%) developed hematological secondary malignancies with a predominance of B-lymphoid neoplasms.

Conclusion: Long-term overall survival in HCL patients treated with sc Cld was excellent and comparable to studies using iv Cld. Despite the long follow-up, sc Cld had a curative potential and relapses requiring re-treatment were observed only in a minority of patients. Secondary malignancies were predominantly non-hematological. These data indicate that patients need to be followed carefully with a special focus on secondary malignancies.

Disclosures

Chalandon:Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel costs.

Author notes

*

Asterisk with author names denotes non-ASH members.

Sign in via your Institution