Rituximab as frontline monotherapy in untreated hairy cell leukemia patients

Abstract

Rituximab as frontline monotherapy in untreated hairy cell leukemia patientsWe have read with great interest the recent article by Leclerc et al. [1] assessing rituximab therapy in hairy cell leukemia, following recent guidelines upon its usage in combination with or without purine analogs in relapsed/refractory disease [2,3]. The authors [1] make an important statement concerning the scarce data upon the use of frontline rituximab as monotherapy, in patients unable to receive other agents due to associated cytopenias, progressive disease, patients who are very elderly, and/or have a poor performance status. Of note in the latter group, attending physicians are not uncommonly met with patients with second malignancy including the solid organ, skin, and lymphoid neoplasms, as shown in large epidemiological studies [4].We hereby would like to report our recent experience with a 70-year-old male patient admitted to our department with shortness of breath in the context of a newly diagnosed pleural effusion (Fig. 1a) for further evaluation. Initial investigation revealed mild pancytopenia (WBC, 2.20 K/μl; poly, 46 %; lymph, 52 %; mono, 2 %; PLT, 135.00 K/μl; Hb, 11.5 g/dl) in the presence of hairy cells in peripheral blood smear, along with several nodular lesions of nonspecific characteristics, approximately~1 cm at the top and posterior segments of the right and left lungs (Fig. 1b). Bone marrow trephine biopsy confirmed 40-50 % lymphocyte infiltration (Fig. 1c, d), the great majority being strongly positive for CD20 (Fig. 1e) and less for CD79a, while 15 % of cells were positive for DBA44 (Fig. 1f). Immunophenotypic analysis of peripheral blood revealed a small CD103(+) population, supporting the diagnosis of B hairy cell leukemia. However, fine needle biopsy staining of pulmonary lesions was positive for TTF-1 and surfactant apoprotein, leading to the diagnosis of synchronous adenocarcinoma of the lung. A PET-CT scan confirmed lesions in the right and left upper lung fields, together with abnormal signal along the right pleura, spleen, and right scapula, along with a newly identified right axillary lymph node. Due to the second malignancy and existing cytopenias, we decided to treat this patient with rituximab alone. He received a weekly course of rituximab (375 mg/m 3 ) for 4 weeks, followed by five monthly courses. Marked increase and complete normalization of blood count were noted after the first 4 cycles and the end of therapy, respectively. A month following the end of the last course, bone marrow trephine biopsy confirmed complete remission of hairy cell leukemia; hence, the patient went on to receive chemotherapy for his lung cancer.Including ours, 12 cases of frontline rituximab monotherapy, the majority of which due to existing neutropenia have been recorded in the literature [1, 5-7] receiving approximately 4-8 weekly infusions. Forty-two percent of patients (5/12) achieved some response [5][6][7], while in 58 % (7/12) of patients, complete remission was noted ranging from 1 to

Prompt Hematological Recovery in Response to a Combination of Pegylated Interferon α-2a and Rituximab in a Profoundly Immuno-Suppressed Hairy Cell Leukemia Patient with a Mycobacterial Infection at Onset: Benefits and Drawbacks of Rapid Immune Reconstitution

“…A small number of cases of frontline rituximab monotherapy have been recorded in the literature, with CR reported in 58% of patients [ 15 ]. Of note, rituximab retreatment has been reported to be effective [ 13 ].…”

Potential breakthroughs with investigational drugs for hairy cell leukemia

“…Rituximab can be given as a single agent or in combination with purine nucleoside analogs. Although rituximab is associated with an OR in up to 80% of relapsed or refractory patients when used alone, other studies have demonstrated less spectacular results [52][53][54][55][56][57][58]. In several studies, rituximab was given at a dose of 375 mg/m 2 weekly for 4 --8 weeks.…”

“…In a study by Nieva et al for patients relapsing after cladribine, four doses of rituximab produced 25% of overall response (OR) rate, only half being CRs [53]. There are only few reports on the use of rituximab alone as frontline therapy in previously untreated HCL patients [53,[56][57][58][59]. One study reports that 58% (7/12) of HCL patients, who were previously untreated mainly due to existing neutropenia, obtained CR ranging from 1 to 54 months after receiving 4 --8 weekly infusions of rituximab monotherapy.…”

Are Cladribine and Rituximab Enough for the Treatment of Relapsed Hairy Cell Leukemia?

“…This is the reason for which our patient was treated with alpha-interferon, which was also indicated due to the presence of severe neutropenia and the presence of fever. Rituximab could be used instead of interferon, 375 mg/m 2 IV per week, during a month, as frontline monotherapy [3,14], but it was not invented at that time. The response rate was only 82 % (with 59 % complete hematological remissions) when it was used alone [15].…”