Safety and efficacy of bortezomib‐based regimens for multiple myeloma patients with renal impairment: a retrospective study of Italian Myeloma Network GIMEMA

Abstract

Renal impairment (RI) is a severe complication throughout the course of multiple myeloma (MM). Bortezomib has been shown to be highly active in MM patients with RI. We designed this retrospective analysis to investigate the safety and efficacy of bortezomib-based therapy in 117 MM patients with RI, 14 cases required dialysis. A total of 603 cycles of bortezomib were administered (median number, five cycles/patient). Ten patients required early discontinuation of bortezomib because of WHO grade IV toxicity. The rate of bortezomib discontinuation in cases with severe, moderate and mild RI was 11%, 5% and 0%, respectively (P = NS). Overall, 91 episodes of WHO grade III/IV toxicity were observed. At least a partial response was documented in 83/113 evaluable patients (73%), including complete response (19%) and near complete response (8%). The overall response rate was similar across RI subgroups. Reversal of RI was documented in 41% of patients after a median of 2.3 months (range 0.4-7.9). In three of 14 patients on dialysis, renal replacement therapy was discontinued after 1, 1 and 4 months. The 2-yr estimate of response duration and overall survival was 70% and 51%, respectively. In conclusion, bortezomib-based regimens are safe and effective and should be considered as appropriate treatment options for MM patients with any degree of RI.

Limiting early mortality: Do's and don'ts in the management of patients with newly diagnosed multiple myeloma

“…Similarly, the analysis of a cohort of patients with glomerular filtration rate <50 mL/min entering the VISTA trial revealed 44% of renal responses in the VMP arm vs. 34% in the MP arm [25]. Many other series demonstrated partial or complete reversal of renal impairment with bortezomib or bortezomibcontaining regimens [26][27][28][29][30]. Retrospective data are also available demonstrating reversibility of RI in regimens containing immunomodulatory drugs [31].…”

A Young Patient with Refractory Multiple Myeloma and Dialysis-Dependent Renal Failure has been Cured by Non-Cryopreserved Autologous Stem Cell Transplantation Followed by Live-Related Kidney Transplantation

“…Renal impairment is a common complication of MM [34][35][36][37]. Between 30% and 50% of patients with newly diagnosed MM present with renal dysfunction while renal failure occurs in approximately 20%-30% of patients with MM at diagnosis and in more than 50% of patients with advanced disease.…”

“…Even in MM patients having dialysis-dependent renal failure, bortezomib-based regimens can be safely used and can potentially reverse renal function and contribute to the improvement in outcome [35,39,42,43]. Bortezomib and high-dose dexamethasone regimen is considered the regimen of choice in patients with MM presenting with severe renal dysfunction or failure [34,38].…”

Dialysis-dependent renal failure in patients with multiple myeloma: Reversibility factors

“…Эффек-тивность содержащих бортезомиб программ в достиже-нии гематологического ответа составляет 75-95% [12,[15][16][17]. Помимо противоопухолевого действия бортезо-миб ингибирует синтез нуклеарного фактора κB, важней-шего медиатора в развитии почечного интерстициального воспаления и фиброза.…”

“…Однако достижение гематологиче-ского ответа не всегда сопровождается улучшением функ-ции почек и во многом зависит от исходной степени тяже-сти ПН. Если при начальной и умеренной стадии ПН при скорости клубочковой фильтрации (СКФ) более 30 мл/мин, ПочО отмечается в 78% случаев, то при тяжелой ее стадии (СКФ менее 30 мл/мин) -в 27-37%, а у больных на ГД -лишь у 20-29% [12,15,18]. Таким образом, несмотря на применение высокоэффективных программ лечения, обратимость диализзависимой ПН остается низкой.…”