[HTML][HTML] A phase II trial of pan-KIR2D blockade with IPH2101 in smoldering multiple myeloma

N Korde, M Carlsten, MJ Lee, A Minter, E Tan… - …, 2014 - ncbi.nlm.nih.gov
N Korde, M Carlsten, MJ Lee, A Minter, E Tan, M Kwok, E Manasanch, M Bhutani, N Tageja
Haematologica, 2014ncbi.nlm.nih.gov
Table 1. Patients' characteristics and results. This phase II clinical trial was open for SMM
patients (serum M-protein≥ 3 g/dL and/or bone marrow plasma cells≥ 10% and absence of
end organ damage). The study was planned as a single arm Simon 2-stage design where
the first 9 patients were enrolled and monthly responses evaluated after receiving 6 cycles of
IPH2101. A cycle was defined as being completed 2 months after the last IPH2101 infusion.
If 3 or more patients achieved a 50% reduction in M-protein, the study was designed to go …
Table 1. Patients’ characteristics and results. This phase II clinical trial was open for SMM patients (serum M-protein≥ 3 g/dL and/or bone marrow plasma cells≥ 10% and absence of end organ damage). The study was planned as a single arm Simon 2-stage design where the first 9 patients were enrolled and monthly responses evaluated after receiving 6 cycles of IPH2101. A cycle was defined as being completed 2 months after the last IPH2101 infusion. If 3 or more patients achieved a 50% reduction in M-protein, the study was designed to go into a second stage to enroll a total of 21 patients. After completion of the first stage interim analysis, the study was terminated due to the lack of patients meeting the defined primary objective (50% decline in M-protein). Current disease status reported after median follow up of 32 months (range 8-37). Clinical progressive disease to MM was based on the IMW criteria for MM. 6 In addition to standard criteria for progressive disease, patients were monitored for biochemical progression (asymptomatic,≥ 25% M-protein increase from baseline and an absolute increase of M-protein of 0.75 g/dL demonstrated on two separate occasions). Patients# 2, 3, 4, 6, 7, and 8 remain asymptomatic with SMM. Patient# 6 (MR) demonstrated a 33% decline of base-line M-protein and a 50% decline in CD138+ plasma cells compared to baseline. Of note, the patient suffered an asthma flare requiring a brief course of systemic steroids (50 mg of prednisone for 14 days during cycle 4). Given the sustained response for 6 months and objective decline in M-protein and CD138+ bone marrow plasma cells, the patient received an additional 6 cycles of IPH2101. This patient continues to have no evidence of clinical symptomatic MM, however his subsequent treatment with IPH2101 was again confounded by another short course of steroids for arthritis. Patient# 4 with biochemical progression remains asymptomatic with SMM. Patient# 1 had clinical progression and was treated for newly diagnosed MM. Patients 5 and 9 had clinical progression during the follow up period and were treated for newly diagnosed MM. The median baseline (pre-treatment) absolute KIR2D SP NK cell counts were compared in patients who had stable disease (SD) or a minimal response (MR)(13.8 cells/mL) versus those who had progressive disease (PD) or biochemical progression (BP)(14.6 cells/mL) during the trial or at follow up with no difference found between the two groups using a Mann-Whitney test (P= 0.56)(Figure not shown).
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