Leukemia & Lymphoma, June 2011; 52(S2): 75–78
Rituximab with pentostatin or cladribine: an effective combination treatment for hairy cell leukemia after disease recurrence
MONICA ELSE1, CLAIRE E. DEARDEN1, ESTELLA MATUTES1, FRANCESCO FORCONI2, FRANCESCO LAURIA2, HUMAYUN AHMAD3, SUSAN KELLY4, ANANDIKA LIYANAGE5, VIJITHA RATNAYAKE5, JAGADEESAN SHANKARI6, IOANA WHALLEY7,& DANIEL CATOVSKY1
1The Institute of Cancer Research and the Royal Marsden NHS Trust, Sutton, UK, 2Ematologia e Trapianti, Dipartimento di Medicina clinica e Scienza Immunologiche, Universita
` degli studi di Siena – AOUS, Siena, Italy, 3Burton Hospitals NHS
Trust, Burton upon Trent, UK, 4Buckinghamshire Hospitals NHS Trust, High Wycombe, UK, 5East Kent Hospitals University NHS Foundation Trust, Ashford, Kent, UK, 6Basildon and Thurrock University Hospitals NHS Foundation Trust, Basildon, UK, and 7The Ipswich Hospital NHS Trust, Ipswich, UK
Abstract The purine analogs pentostatin and cladribine are effective treatments for hairy cell leukemia (HCL). However, alternative treatments are needed for patients with recurrent disease. We reviewed retrospectively data from 18 patients who were
retreated with either pentostatin (n¼12) or cladribine (n¼6) in combination with rituximab, after 1–6 (median 2) previous treatments with either purine analog as a single agent. All 18 patients responded to therapy, with a complete response (CR) rate of 89%. This compared favorably with CR rates of 68% after second-line therapy and 47% after third-line therapy in 88 patients retreated one or more times with a purine analog alone. Toxicity with the combination treatment was minimal. At a median follow-up of 36 months (range 5–83 months) all 16 complete responders remained in CR, while one partial responder developed recurrent disease at 10 months. The estimated recurrence rate at 3 years was 7%. This compares with 21% after second-line therapy and 42% after third-line therapy in the 88 patients retreated with a purine analog alone. Furthermore, it was a marked improvement on the 55% recurrence at 3 years previously seen in these same 18 patients after
their own first-line treatment with single-agent pentostatin or cladribine (p¼0.006). The combination of a purine analog with rituximab was safe and effective for patients with recurrent HCL. The results suggest an added benefit compared with single-agent purine analog therapy.
Keywords: Hairy cell leukemia, rituximab, pentostatin, cladribine Introduction
The purine analogs pentostatin and cladribine have revolutionized the treatment of hairy cell leukemia (HCL), with overall responses in more than 85% of patients and median relapse-free survival of up to 16 years [1–7]. They continue to be effective at second- and even third-line therapy; however, both the complete response (CR) rate and the disease-free survival rate decline with each successive line of treatment [7,8]. Achieving a CR, at any line of
therapy, is associated with longer disease-free survi- val [2–7], and alternative treatments are therefore needed for patients who have previously responded poorly to single-agent purine analogs or have required multiple lines of therapy. The antigen CD20 is highly expressed on hairy cells [9] and consequently the anti-CD20 monoclonal antibody rituximab has efficacy in HCL, particularly when used in combination with a purine analog [9,10]. The present study, updating our previous reports [7,11], examined the efficacy and safety of this
Correspondence: Professor Daniel Catovsky, Section of Haemato-Oncology, Institute of Cancer Research, Cotswold Road, Sutton SM2 5NG, United Kingdom. Tel: þ44(0)208-722-4461. Fax: þ44(0)20-8722-4432. E-mail:
daniel.catovsky@
icr.ac.uk
ISSN 1042-8194 print/ISSN 1029-2403 online 2011 Informa UK, Ltd. DOI: 10.3109/10428194.2011.568650
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100 |
Page 101 |
Page 102 |
Page 103 |
Page 104 |
Page 105 |
Page 106 |
Page 107 |
Page 108 |
Page 109 |
Page 110 |
Page 111 |
Page 112 |
Page 113 |
Page 114 |
Page 115 |
Page 116 |
Page 117 |
Page 118 |
Page 119 |
Page 120 |
Page 121 |
Page 122