Hematologic and renal improvement of monoclonal immunoglobulin deposition disease after treatment with bortezomib-based regimens

Abstract

Monoclonal immunoglobulin deposition disease (MIDD) is characterized by non-organized immunoglobulin-fragments along renal basement membranes with subsequent organ deterioration. Treatment is directed against the immunoglobulin-producing clone. We treated 18 MIDD patients with bortezomib-based regimens (12 received bortezomib-dexamethasone, 6 bortezomib-dexamethasone with cyclophosphamide). Eleven (61%) patients achieved a hematologic response, but only 6 (33.3%) reached to a complete (CR) or very good partial response (VGPR). Regarding renal outcomes 77.8 and 55.6% had ≥30 and ≥50% reduction of proteinuria, respectively, but 33.3% ended up in end-stage renal disease (ESRD). Among patients with CR or VGPR, median eGFR improvement was 7.7 ml/min/1.73 m and none progressed to ESRD, but no significant renal recovery was observed in patients achieving a partial response or less, with 50% progressing to dialysis. Pretreatment eGFR seems to influence renal prognosis. Bortezomib-based treatment is considered an effective approach in MIDD and reaching to a deep hematologic response (≥VGPR) conditionally controls further renal declining.

Long term outcomes in monoclonal gammopathy of renal significance

“…Similarly, although there was no effect of bortezomibbased therapy on RS detected, improved RS following bortezomib has previously been observed in other MGRS studies (Cohen et al, 2015;Sayed et al, 2015;Li et al, 2016;Chauvet et al, 2017;Ziogas et al, 2017). This may be explained by the confounding effect of CKD stage, because patients with more advanced kidney disease at diagnosis were more likely to receive clone-directed treatment at an earlier time point along their disease course.…”

Monoclonal Gammopathy of Renal Significance: Consensus of Hematologists and Nephrologists of Russia on the Establishment of Nosology, Diagnostic Approach and Rationale for Clone Specific Treatment

“…Признание зарубежными медицинскими сообществами, в том числе Международной рабочей группой по миеломе (International Myeloma Working Group) [18], взаимосвязи клона и поражения почек -моноклональной гаммапатии ренального значения -открыло возможность назначения таким пациентам высокоэффективной химиотерапии. Терапевтическое воздействие, направленное на подавление клона, оказалось эффективным как в отношении почечных исходов, так и общей выживаемости [7,9,[12][13][14].…”

Dysproteinemias and Glomerular Disease

“…Fortunately, the hematologic response can be improved by the addition of autologous stem cell transplant. Achievement of VGPR in monoclonal Ig deposition disease similarly has been found to improve renal and patient survival (21,42,74,89). Kidney transplant has been successfully performed in patients with hematologic complete response without recurrence.…”

“…Patients with complete response are less likely to have recurrence after kidney transplant (88). Bortezomib seems to be the most effective agent in monoclonal Ig deposition disease (21,42,74,89). In one study, immunomodulatory drugs represented by thalidomide and lenalidomide were found to be less effective in achieving VGPR or better responses (21).…”