Role of light chain clearance in the recovery of renal function in multiple myeloma: another point of view

Lay Summary This is a retrospective multicenter study that evaluated the effectiveness of intensive haemodialysis (IHD) vs standards dialysis on renal recovery in patients with acute kidney injury (AKI) associated with myeloma multiple (MM). In this paper, we demonstrated that IHD for early light chain reduction was associated with a better renal prognosis. Another finding is the importance of maintenance diuresis as a marker of good prognosis of renal function. To our knowledge few studies have been focused in the comparison between IHD vs standard dialysis in MM patients with AKI. We consider that if we manage to recover the renal function, we achieve a great clinical impact since the patient with chronic kidney disease and especially in hemodialysis, an increased risk of mortality as well as poorer quality of life. Background Acute kidney injury (AKI) in patients with multiple myeloma (MM) requiring renal replacement treatment (RRT) is associated with high morbidity and mortality. Early reduction of serum free light chains (FLC) using both targeted therapy against MM and intensive hemodialysis (IHD) may improve renal outcomes. We evaluated the effectiveness of two different RRT techniques on renal recovery in an MM patient population: standard dialysis procedure vs IHD with either polymethylmethacrylate (PMMA) or hemodiafiltration with endogenous reinfusion (HFR). Methods This was a multicentric retrospective study with severe AKI related to MM, between 2011 and 2018. Twenty-five consecutive patients with AKI secondary to MM requiring RRT were included. Patients that underwent IHD received six dialysis sessions per week during the first 14 days (PMMA vs HFR). All patients were diagnosed with de novo MM or first relapsed MM. Primary outcome was renal recovery defined as dialysis-free at 6 months follow-up. Results A total of 25 patients were included. Seventeen patients received IHD and eight standard dialysis. All patients were treated with targeted therapy, 84% bortezomib-based. Of the 25 patients included, 14 (56%) became dialysis independent. We observed a higher proportion of patients who received IHD in the group who recovered kidney function compared with those who remained in HD (92.9% vs 36.4%, P = .007). In our study, the use of IHD to remove FLC had a statistically significant association with renal recovery compared with the standard dialysis group (P = .024). Conclusion Early reduction of FLC with IHD as an adjuvant treatment along with MM-targeted therapy may exert a positive impact on renal recovery

Multiple myeloma and SARS-CoV-2 infection: clinical characteristics and prognostic factors of inpatient mortality

There is limited information on the characteristics, prognostic factors, and outcomes of patients with multiplemyeloma (MM) hospitalized with COVID-19. This retrospective case series investigated 167 patients reported from 73hospitals within the Spanish Myeloma Collaborative Group network in March and April, 2020. Outcomes werecompared with 167 randomly selected, contemporary, age-/sex-matched noncancer patients with COVID-19 admittedat six participating hospitals. Among MM and noncancer patients, median age was 71 years, and 57% of patients weremale; 75 and 77% of patients, respectively, had at least one comorbidity. COVID-19 clinical severity wasmoderate-severe in 77 and 89% of patients and critical in 8 and 4%, respectively. Supplemental oxygen was requiredby 47 and 55% of MM and noncancer patients, respectively, and 21%/9% vs 8%/6% required noninvasive/invasiveventilation. Inpatient mortality was 34 and 23% in MM and noncancer patients, respectively. Among MM patients,inpatient mortality was 41% in males, 42% in patients aged >65 years, 49% in patients with active/progressive MM athospitalization, and 59% in patients with comorbid renal disease at hospitalization, which were independentprognostic factors on adjusted multivariate analysis. This case series demonstrates the increased risk and identifiespredictors of inpatient mortality among MM patients hospitalized with COVID-19

Multiple myeloma and SARS-CoV-2 infection : clinical characteristics and prognostic factors of inpatient mortality

There is limited information on the characteristics, prognostic factors, and outcomes of patients with multiple myeloma (MM) hospitalized with COVID-19. This retrospective case series investigated 167 patients reported from 73 hospitals within the Spanish Myeloma Collaborative Group network in March and April, 2020. Outcomes were compared with 167 randomly selected, contemporary, age-/sex-matched noncancer patients with COVID-19 admitted at six participating hospitals. Among MM and noncancer patients, median age was 71 years, and 57% of patients were male; 75 and 77% of patients, respectively, had at least one comorbidity. COVID-19 clinical severity was moderate-severe in 77 and 89% of patients and critical in 8 and 4%, respectively. Supplemental oxygen was required by 47 and 55% of MM and noncancer patients, respectively, and 21%/9% vs 8%/6% required noninvasive/invasive ventilation. Inpatient mortality was 34 and 23% in MM and noncancer patients, respectively. Among MM patients, inpatient mortality was 41% in males, 42% in patients aged >65 years, 49% in patients with active/progressive MM at hospitalization, and 59% in patients with comorbid renal disease at hospitalization, which were independent prognostic factors on adjusted multivariate analysis. This case series demonstrates the increased risk and identifies predictors of inpatient mortality among MM patients hospitalized with COVID-19

MM, SARS-CoV-2 infection, and inpatient mortality

There is limited information on the characteristics, pre-admission prognostic factors, and outcomes of patients with multiple myeloma (MM) hospitalized with coronavirus disease 2019 (COVID-19). This retrospective case series investigated characteristics and outcomes of 167 MM patients hospitalized with COVID-19 reported from 73 hospitals within the Spanish Myeloma Collaborative Group network in Spain between March 1 and April 30, 2020. Outcomes were compared with a randomly selected contemporary cohort of 167 age-/sex-matched non-cancer patients with COVID-19 admitted at 6 participating hospitals. Common demographic, clinical, laboratory, treatment, and outcome variables were collected; specific disease status and treatment data were collected for MM patients. Among the MM and non-cancer patients, median age was 71 years and 57% of patients were male in each series, and 75% and 77% of patients, respectively, had at least one comorbidity. COVID-19 clinical severity was moderate-severe in 77% and 89% of patients and critical in 8% and 4%, respectively. Supplemental oxygen was required by 47% and 55% of MM and non-cancer patients, respectively, and 21%/9% vs 8%/6% required non-invasive/invasive ventilation. Inpatient mortality was 34% and 23% in MM and non-cancer patients, respectively. Among MM patients, inpatient mortality was 41% in males, 42% in patients aged >65 years, 49% in patients with active/progressive MM at hospitalization, and 59% in patients with comorbid renal disease at hospitalization, which were independent prognostic factors of inpatient mortality on adjusted multivariate analysis. This case series demonstrates the increased risk and identifies predictors of inpatient mortality among MM patients hospitalized with COVID-19.This study was supported by PETHEMA FoundationN

Multiple myeloma and SARS-CoV-2 infection: clinical characteristics and prognostic factors of inpatient mortality

There is limited information on the characteristics, prognostic factors, and outcomes of patients with multiple myeloma (MM) hospitalized with COVID-19. This retrospective case series investigated 167 patients reported from 73 hospitals within the Spanish Myeloma Collaborative Group network in March and April, 2020. Outcomes were compared with 167 randomly selected, contemporary, age-/sex-matched noncancer patients with COVID-19 admitted at six participating hospitals. Among MM and noncancer patients, median age was 71 years, and 57% of patients were male; 75 and 77% of patients, respectively, had at least one comorbidity. COVID-19 clinical severity was moderate–severe in 77 and 89% of patients and critical in 8 and 4%, respectively. Supplemental oxygen was required by 47 and 55% of MM and noncancer patients, respectively, and 21%/9% vs 8%/6% required noninvasive/invasive ventilation. Inpatient mortality was 34 and 23% in MM and noncancer patients, respectively. Among MM patients, inpatient mortality was 41% in males, 42% in patients aged >65 years, 49% in patients with active/progressive MM at hospitalization, and 59% in patients with comorbid renal disease at hospitalization, which were independent prognostic factors on adjusted multivariate analysis. This case series demonstrates the increased risk and identifies predictors of inpatient mortality among MM patients hospitalized with COVID-19

KarMMa-RW: comparison of idecabtagene vicleucel with real-world outcomes in relapsed and refractory multiple myeloma.

Patients with relapsed and refractory multiple myeloma (RRMM) who are triple-class exposed (to an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody) have limited treatment options and there is no standard of care. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T-cell therapy, demonstrated efficacy in triple-class exposed RRMM patients in the KarMMa trial (NCT03361748). In this retrospective study (KarMMa-RW), patient-level data from triple-class exposed RRMM patients were merged into a single data model and compared with KarMMa using trimmed stabilized inverse probability of treatment weighting. Endpoints included overall response rate (ORR; primary), rate of very good partial response or better (≥VGPR), progression-free survival (PFS), and overall survival (OS). Of 1949 real-world triple-class exposed RRMM patients, 190 received subsequent (index) line of therapy and met KarMMa eligibility criteria (Eligible RRMM cohort). With a median follow-up of 13.3 months in KarMMa and 10.2 months in Eligible RRMM, ORR, and ≥VGPR were significantly improved in KarMMa versus Eligible RRMM (ORR, 76.4% vs 32.2%; ≥VGPR, 57.9% vs 13.7%; both P < 0.0001) as were PFS (11.6 vs 3.5 months; P = 0.0004) and OS (20.2 vs 14.7 months; P = 0.0006). This study demonstrated that ide-cel significantly improved responses and survival compared with currently available therapies in triple-class exposed RRMM

KarMMa-RW: comparison of idecabtagene vicleucel with real-world outcomes in relapsed and refractory multiple myeloma.

Patients with relapsed and refractory multiple myeloma (RRMM) who are triple-class exposed (to an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody) have limited treatment options and there is no standard of care. Idecabtagene vicleucel (ide-cel, bb2121), a BCMA-directed CAR T-cell therapy, demonstrated efficacy in triple-class exposed RRMM patients in the KarMMa trial (NCT03361748). In this retrospective study (KarMMa-RW), patient-level data from triple-class exposed RRMM patients were merged into a single data model and compared with KarMMa using trimmed stabilized inverse probability of treatment weighting. Endpoints included overall response rate (ORR; primary), rate of very good partial response or better (≥VGPR), progression-free survival (PFS), and overall survival (OS). Of 1949 real-world triple-class exposed RRMM patients, 190 received subsequent (index) line of therapy and met KarMMa eligibility criteria (Eligible RRMM cohort). With a median follow-up of 13.3 months in KarMMa and 10.2 months in Eligible RRMM, ORR, and ≥VGPR were significantly improved in KarMMa versus Eligible RRMM (ORR, 76.4% vs 32.2%; ≥VGPR, 57.9% vs 13.7%; both P < 0.0001) as were PFS (11.6 vs 3.5 months; P = 0.0004) and OS (20.2 vs 14.7 months; P = 0.0006). This study demonstrated that ide-cel significantly improved responses and survival compared with currently available therapies in triple-class exposed RRMM

Multiple myeloma and SARS-CoV-2 infection: clinical characteristics and prognostic factors of inpatient mortality

There is limited information on the characteristics, prognostic factors, and outcomes of patients with multiple myeloma (MM) hospitalized with COVID-19. This retrospective case series investigated 167 patients reported from 73 hospitals within the Spanish Myeloma Collaborative Group network in March and April, 2020. Outcomes were compared with 167 randomly selected, contemporary, age-/sex-matched noncancer patients with COVID-19 admitted at six participating hospitals. Among MM and noncancer patients, median age was 71 years, and 57% of patients were male; 75 and 77% of patients, respectively, had at least one comorbidity. COVID-19 clinical severity was moderate–severe in 77 and 89% of patients and critical in 8 and 4%, respectively. Supplemental oxygen was required by 47 and 55% of MM and noncancer patients, respectively, and 21%/9% vs 8%/6% required noninvasive/invasive ventilation. Inpatient mortality was 34 and 23% in MM and noncancer patients, respectively. Among MM patients, inpatient mortality was 41% in males, 42% in patients aged >65 years, 49% in patients with active/progressive MM at hospitalization, and 59% in patients with comorbid renal disease at hospitalization, which were independent prognostic factors on adjusted multivariate analysis. This case series demonstrates the increased risk and identifies predictors of inpatient mortality among MM patients hospitalized with COVID-19.Peer reviewe