Phase 2 study of cladribine followed by rituximab in patients with hairy cell leukemia

Abstract

We conducted this study to determine the feasibility and safety of cladribine followed by rituximab in patients with hairy cell leukemia including the variant form (HCLv). Cladribine 5.6 mg/m 2 given IV over 2 hours daily for 5 days was followed ϳ 1 month later with rituximab 375 mg/m 2 IV weekly for 8 weeks.Responses were recorded and BM minimal residual disease (MRD) was evaluated after the completion of rituximab. Thirty-six patients have been treated in- IntroductionOver the past quarter century, we have witnessed remarkable progress in the treatment of patients with hairy cell leukemia (HCL). 1,2 The nucleoside analogs cladribine and pentostatin have made a significant impact in the treatment of HCL producing complete response (CR) rates of 80% to 90%. 3,4 Long-term follow-up of patients treated with these agents have shown that about one-fourth to one-third of patients relapse after a follow-up of 3 to 4 years with little difference between the 2 drugs, in terms of durability of response. [5][6][7] Previous reports have suggested that the quality of the initial response can be predictive of the outcome, with a longer disease-free survival in those achieving a CR after initial therapy as opposed to those with lesser responses. [7][8][9] This has led to the suggestion by some authors to persist with therapy, in the absence of toxicity, until a CR is attained, 7 and to efforts to eradicate minimal residual disease (MRD) after the initial therapy. This is particularly important as the median age of patients with HCL is in the 50s, and subsequent CRs may be shorter in duration with successive therapy. 5,10,11 Determination of the risk of relapse based on the persistence of MRD determined by immunohistochemistry (IHC) using anti-CD45RO, anti-CD20, and DBA.44 in paraffin-embedded BM sections was first reported by the group from Northwestern University. 12 More recently, more precise methods using immunophenotyping by flow cytometry, and consensus primer or clonespecific PCR analysis of Ig receptors, have been used to detect MRD in patients with HCL. [13][14][15] Whether eradication of MRD should be a goal of therapy in the initial management of patients with HCL remains a subject of discussion. 16 Sigal et al have reported that among 19 patients with HCL in continuous CR after 1 course of cladribine (median time from therapy, 16 years, [range, 11-21 years]) in whom BM samples were available, 7 (37%) had MRD, and 3 (16%) had morphologic evidence of HCL suggesting that patients with MRD or even morphologic disease can live many years without a hematologic relapse. 17 We have previously reported on the efficacy of rituximab in eradicating MRD in patients with HCL treated with cladribine. 14 Among the 13 patients, reported MRD assessed by consensus primer PCR or flow cytometry was eradicated in 92% at 3 months. We have reported a brief summary of this phase 2 trial including patients with relapsed disease recently for a collective report of a meeting of hairy cell leukemia experts at the National Institutes of Heal...

Rituximab therapy for hairy cell leukemia: a retrospective study of 41 cases

“…The longest follow-up in our cohort (median 45 months for these patients) may explain this difference. However, even in case of combination with PA, relapse rate in our study (11 % after a median follow-up of 24.5 months) is still higher than published data, although to a lesser extent [15,16].…”

“…Whereas the largest series published to date concerns the use of rituximab in combination with PA for frontline therapy of HCL [14,15], this situation represents only 5 of the 49 treatments reported in our study, with an excellent treatment outcome (100 % CHR). Most of our patients were treated at relapse, after multiple courses of therapy and a median time of more than 6 years since HCL diagnosis.…”

“…These encouraging results have led to combine rituximab with PA, both in previously untreated and in relapsed patients. As frontline therapy, combination with cladribine provided an impressive 100 % response rate in two separate cohorts that included a total of 63 patients [14,15]. Moreover, molecular responses were obtained in 70 % of these patients.…”

My Treatment Approach to Hairy Cell Leukemia

“…These researchers updated their experience in 45 HCL patients, 38 with untreated disease. 37 In 24% of patients, MRD was detected at the completion of cladribine and rituximab treatment. These studies demonstrate the effectiveness of rituximab in reducing or eradicating MRD.…”

Orphan drugs for the treatment of hairy cell leukemia

“…In contrast to the purine analogs, responses to Rituximab are achieved in 30 --50% of patients and less than 20% are CR. By contrast the combination of chemoimmunotherapy (Rituximab plus DCF or CDA) in patients who experience early relapse, multiple relapses or do not achieve a response to single agent purine analog demonstrates that this combination is highly effective [69,70]. Else et al reported the efficacy of a combination of DCF or CDA with Rituximab in eight multiple relapsed or refractory HCL patients with impressive results [69].…”