Rituximab treatment provides no clinical benefit in patients with pretreated advanced multiple myeloma

Abstract

In the present phase II study, we tested the efficacy of a single course of rituximab (375 mg/m2 on days 1, 8, 15 and 22) as treatment for relapsed myeloma. The rationale for this study was the identification of a population of clonotypic CD20+ B cells that are believed to be precursors of malignant plasma cells. In addition, CD20 was expressed on 10% and 50% of bone marrow plasma cells in two of the ten patients enrolled. Following rituximab treatment, none of the patients achieved an objective response. Two patients had stable disease at month 6, the predefined end of the study, while, at that time, two patients were classified as having progressive disease. One patient opted to withdraw from the study at month 3, at which time he had stable disease. The other five patients had to be withdrawn early from the post-treatment observation because of need of salvage therapy for progressive disease. WHO grade <or=2 toxicity was seen in four patients. Peripheral B cells significantly decreased at 3 months, while no significant change of bone marrow myeloma cells was noted at that time. Mean paraprotein levels increased slightly during follow-up but IgM levels dropped in all patients, indicating an effective targeting of normal, short-lived plasma cells. Taken together, rituximab treatment yielded significant reductions in circulating B cells and serum IgM levels but had no beneficial clinical effect.

Reply to Rituximab activity in CD20 positive multiple myeloma

“…In the previous trials, patients with CD20 þ MM did not show a response to rituximab, but they were not selected according to CD20 expression. 2,3 In fact, as correctly reported by the authors, several factors have been described to explain resistance against rituximab in a variety of B-cell malignancies such as the level of CD20 expression, dissociated action of complement-dependent cytotoxicity and antibodydependant cellular cytotoxicity. These mechanisms could explain the marginal activity of rituximab as single agent in CD20 þ MM, and introduce the idea that timing of administration (especially after high-dose therapy regimens) also could be useful in reducing minimal residual disease.…”

“…These frequencies were in the range of previous studies. [1][2][3] CMML showed a lower frequency of JAK2V617F with 5/27 cases (18.5%). In AML, the overall JAK2 mutation rate of all analyzed AML cases was not calculated because this group was selected showing an overrepresention of s-AML after CMPD.…”

“…Owing to the high incidence of the V617F point mutation in the JAK2 gene on 9p24 in the BCR-ABL-negative chronic myeloproliferative diseases (CMPD), molecular screening for the respective mutation achieved a key role for patients with polycythemia vera (PV), essential thrombocytosis (ET), chronic idiopathic myelofibrosis (CIMF) and in cases with the suspicion of a CMPD. [1][2][3] The mutation was further detected in some cases of chronic myelomonocytic leukemia (CMML), 1,3,4 and was reported in acute myeloid leukemia (AML) in lower frequencies, but the number of analyzed cases so far is limited. 1,3,[5][6][7] In addition, the association of JAK2V617F to certain cytogenetic aberrations remains to be clarified.…”

“…[1][2][3] The mutation was further detected in some cases of chronic myelomonocytic leukemia (CMML), 1,3,4 and was reported in acute myeloid leukemia (AML) in lower frequencies, but the number of analyzed cases so far is limited. 1,3,[5][6][7] In addition, the association of JAK2V617F to certain cytogenetic aberrations remains to be clarified.…”

Treatment of severe autoimmune hemolytic anemia in B-cell chronic lymphocytic leukemia with alemtuzumab

“…2 Recently, rituximab (anti-CD20) has been used with efficacy in AHAI complicating B-CLL. 3 But relapses are frequent and some patients become refractory. We report the case of a 69-year-old woman who presented B-CLL complicated by AIHA.…”