Predictive role of absolute lymphocyte count in daratumumab-treated patients with relapsed/ refractory multiple myeloma
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background/Aims: Daratumumab has shown an encouraging antitumor effect in patients with multiple myeloma (MM), and was known to alter the immune properties by off-targeting immunosuppressive cells. Here, we aimed to evaluate the change in absolute lymphocyte count (ALC) as a surrogate marker for predicting survival outcomes of patients treated with daratumumab. Methods: Between 2018 and 2021, the medical records of patients with relapsed/refractory MM (RRMM) treated with daratumumab monotherapy at 10 centers in South Korea were reviewed. We collected the ALC data at pre-infusion (D0), day 2 after the first infusion (D2), and prior to the third cycle of daratumumab therapy (D56). Results: Fifty patients who were administered at least two cycles of daratumumab were included. Overall response rate was 54.0% after two cycles of daratumumab treatment. On D2, almost all patients experienced a marked reduction in ALC. However, an increase in ALC on D56 (ALCD56) was observed in patients with non-progressive disease, whereas failure of ALC recovery was noted in those with progressive disease. Patients with ALCD56 > 700/μL (n = 39, 78.0%) had prolonged progression- free survival (PFS) and overall survival (OS) than those with ALCD56 ≤ 700/μL (median PFS: 5.8 months vs. 2.6 months, p = 0.025; median OS: 24.1 months vs. 6.1 months, p = 0.004). In addition, ALCD56 >700/μL was a significant favorable prognostic factor for PFS (hazard ratio [HR], 0.22; p = 0.003) and OS (HR, 0.23; p = 0.012). Conclusions: Increase in ALC during daratumumab treatment was significantly associated with prolonged survival outcomes in patients with RRMM. The ALC value can predict clinical outcomes in patients treated with daratumumab.
Abstract
Background/Aims: Daratumumab has shown an encouraging antitumor effect in patients with multiple myeloma (MM), and was known to alter the immune properties by off-targeting immunosuppressive cells. Here, we aimed to evaluate the change in absolute lymphocyte count (ALC) as a surrogate marker for predicting survival outcomes of patients treated with daratumumab. Methods: Between 2018 and 2021, the medical records of patients with relapsed/refractory MM (RRMM) treated with daratumumab monotherapy at 10 centers in South Korea were reviewed. We collected the ALC data at pre-infusion (D0), day 2 after the first infusion (D2), and prior to the third cycle of daratumumab therapy (D56). Results: Fifty patients who were administered at least two cycles of daratumumab were included. Overall response rate was 54.0% after two cycles of daratumumab treatment. On D2, almost all patients experienced a marked reduction in ALC. However, an increase in ALC on D56 (ALCD56) was observed in patients with non-progressive disease, whereas failure of ALC recovery was noted in those with progressive disease. Patients with ALCD56 > 700/μL (n = 39, 78.0%) had prolonged progression- free survival (PFS) and overall survival (OS) than those with ALCD56 ≤ 700/μL (median PFS: 5.8 months vs. 2.6 months, p = 0.025; median OS: 24.1 months vs. 6.1 months, p = 0.004). In addition, ALCD56 >700/μL was a significant favorable prognostic factor for PFS (hazard ratio [HR], 0.22; p = 0.003) and OS (HR, 0.23; p = 0.012). Conclusions: Increase in ALC during daratumumab treatment was significantly associated with prolonged survival outcomes in patients with RRMM. The ALC value can predict clinical outcomes in patients treated with daratumumab.
참고문헌 (24)
- Kumar SK, "Improved survival in multiple myeloma and the impact of novel therapies", Blood, 111, pp.2516~2520 (2008)
- Kumar SK, "Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib : a multicenter international myeloma working group study", Leukemia, 26, pp.149~157 (2012)
- Blair HA, "Daratumumab : a review in relapsed and", or refractory multiple myeloma, 2017, pp.77, 2013~2024
- Lokhorst HM, "Targeting CD38with daratumumab monotherapy in multiple myeloma", N Engl J Med, 373, pp.1207~1219 (2015)
- Lonial S, "Daratumumab monotherapy in patients with treatment-refractory multiple myeloma(SIRIUS) : an open-label, randomised, phase 2 trial", Lancet, 387, pp.1551~1560 (2016)
- Usmani SZ, "Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma", Blood, 128, pp.37~44 (2016)
- Facon T, "Daratumumab plus lenalidomide and dexamethasone for untreated myeloma", N Engl J Med, 380, pp.2104~2115 (2019)
- Voorhees PM, "Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma : the GRIFFIN trial", Blood, 136, pp.936~945 (2020)
- Menetrier-Caux C, "Lymphopenia in cancer patients and its effects on response to immunotherapy : an opportunity for combination with cytokines?", J Immunother Cancer, 7, pp.85~ (2019)
- Kim DH, "Clinical impact of early absolute lymphocyte count after allogeneic stem cell transplantation", Br J Haematol, 125, pp.217~224 (2004)
- Siddiqui M, "Absolute lymphocyte count predicts overall survival in follicular lymphomas", Br J Haematol, 134, pp.596~601 (2006)
- De Angulo G, "Absolute lymphocyte count is a novel prognostic indicator in ALL and AML : implications for risk stratification and future studies", Cancer, 112, pp.407~415 (2008)
- Krejcik J, "Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma", Blood, 128, pp.384~394 (2016)
- van de Donk NW, "CD38 antibodies in multiple myeloma : mechanisms of action and modes of resistance", Front Immunol, 9, pp.2134~ (2018)
- Rajkumar SV, "International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma", Lancet Oncol, 15, pp.e538~e548 (2014)
- Kumar S, "International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma", Lancet Oncol, 17, pp.e328~e346 (2016)
- Krejcik J, "Monocytes and granulocytes reduce CD38 expression levels on myeloma cells in patients treated with daratumumab", Clin Cancer Res, 23, pp.7498~7511 (2017)
- Fauci AS, "Glucocorticosteroid therapy : mechanisms of action and clinical considerations", Ann Intern Med, 84, pp.304~315 (1976)
- Kitadate A, "Pre-treatment CD38-positive regulatory T cells affect the durable response to daratumumab in relapsed", refractory multiple myeloma patients, 2020, pp.105, e37~e40
- Ege H, "Prediction of survival using absolute lymphocyte count for newly diagnosed patients with multiple myeloma : a retrospective study", Br J Haematol, 141, pp.792~798 (2008)
- Narwani V, "Absolute lymphocyte count at day 29 of treatment is a powerful predictor of outcome in multiple myeloma", Clin Lymphoma Myeloma Leuk, 15, pp.222~226 (2015)
- Jimenez-Zepeda VH, "Absolute lymphocyte count as predictor of overall survival for patients with multiple myeloma treated with single autologous stem cell transplant", Leuk Lymphoma, 56, pp.2668~2673 (2015)
- Gavriatopoulou M, "The addition of IMiDs for patients with daratumumab-refractory multiple myeloma can overcome refractoriness to both agents", Blood, 131, pp.464~467 (2018)
- Oostvogels R, "Efficacy of retreatment with immunomodulatory drugs and proteasome inhibitors following daratumumab monotherapy in relapsed and refractory multiple myeloma patients", Br J Haematol, 183, pp.60~67 (2018)
