Daratumumab‐based therapy for patients with monoclonal gammopathy of renal significance

Abstract

Treatment of the plasma cell clone in monoclonal gammopathy of renal significance (MGRS) is necessary in order to reduce toxic immunoglobulin load to the kidneys and salvage renal function. There are limited data on the use of daratumumab in patients with MGRS. We summarize our experience with the use of daratumumab-based therapy in 25 MGRS patients, 12 of whom were previously untreated. The median follow-up of the cohort is 14 months. The best overall haematologic response in evaluable patients was complete response (CR) in five (22%), very good partial response (VGPR) in five (22%) and partial response (PR) in seven (30%) patients for an overall response rate of 74%. Two of five patients in CR and two patients with initially detectable clones, but non-measurable immunoglobulins, had undetectable minimal residual disease (MRD) with next-generation flow cytometry (NGF) after therapy. Haematologic response rate for previously untreated patients was 83% vs. 69% for previously treated and for daratumumab combinations it was 91% vs. 64%, and with CR/VGPR 82% vs. 29%, compared to daratumumab monotherapy. At six months, 12/22 (55%) patients not on dialysis achieved a reduction of proteinuria >30%, of at least 0Á5 g/24 h, without an estimated glomerular filtration rate (eGFR) reduction. The toxicity was mild and predictable. In conclusion, daratumumab-based therapy is a new option for patients with MGRS.

Monoclonal Gammopathy of Renal Significance: New Capabilities of Therapy

“…При выборе терапевтической стратегии следует учитывать особенности заболевания почек, такие как риск прогрессирования хронической болезни почек (ХБП), наличие и тяжесть внепочечных проявлений, а также профиль безопасности противоопухолевых лекарственных препаратов при почечной недостаточности. Ранняя диагностика на С1-С3 стадиях ХБП, когда функция почек все еще сохранна, облегчает лечение и улучшает отдаленный прогноз заболевания [27].…”

“…Терапия. 2020; 2 (36): [22][23][24][25][26][27][28][29][30][31][32][33]. DOI: 10.18565/therapy.2020.2.22-33; Смирнов А.В., Афанасьев Б.В., Поддубная И.В.…”

“…обобщен 14-месячный опыт использования терапии на основе даратумумаба у 25 пациентов с MGRS, 12 из которых ранее не получали лечения. Гематологический ответ в данной группе составил 74%: CR был у 5 пациентов (22%), VGPR -у 5 (22%), частичный ответ (PR) -у 7 (30%) [27].…”

“…Через 6 месяцев 55% пациентов, не находившихся на диализе, достигли снижения протеинурии менее чем на 30%, по крайней мере на 0,5 г/сут, без предполагаемого снижения скорости клубочковой фильтрации (СКФ) [27].…”

Daratumumab for Immunoglobulin Light Chain Amyloidosis

“…Daratumumab-based regimens have also been considered for the treatment of the rare entities of monoclonal gammopathies of renal significance, with great efficacy and safety in a small cohort of 25 patients. 65 Although monoclonal antibodies are safe for the treatment of patients with renal dysfunction, in a series of 168 patients with AL amyloidosis treated with daratumumab-based regimens, nephrotic-range proteinuria was an adverse factor for haematological event-free survival. 43 This may be attributed to the impaired glomerular function in patients with severe non-selective proteinuria and to urinary excretion of monoclonal antibodies.…”