Classification of Death Causes after Transplantation (CLASS): Evaluation of Methodology and Initial Results

Abstract

Background. Daratumumab is an IgG kappa monoclonal antibody (mAB) against CD38 which is expressed on myeloma cells. It has recently been approved for treatment of patients with relapsed refractory multiple myeloma. Our objective was to identify the potential infectious complications associated with daratumumab use.Methods. We conducted a retrospective analysis of myeloma patients who received daratumumab at our institution from October 2015 to December 2016. Patients were divided into four groups based on administration regimen of daratumumab: (1) single agent with dexamethasone; (2) triple therapy with proteasome inhibitor (PI), immune-modulating drug (IMiD), mitogen-activated protein kinase (MEK) inhibitor or mAB; (3) quadruple therapy with IMiD + PI ± mAB or cyclophosphamide; (4) with high-dose chemotherapy. For each group, we evaluated the incidence of infection, neutropenia (defined as ANC <1,000), hospitalization, and 90-day survival.Results. A total of 171 patients (63% male, 37% female) were included in the study and received a total of 343 cycles of daratumumab. Median age was 68 years. A total of 151 infections occurred in 121 of the 343 cycles (40% bacterial; 52% viral). There was a significant association between development of infection and chemotherapy regimen used (χ 2 = 17, P ≤ 0.001). Patients developed neutropenia in 129 of 254 cycles (51%). There was a significant association between the development of neutropenia and chemotherapy regimen used (χ 2 = 43.51, P < 0.00001). Discontinuation of chemotherapy occurred in 65 cycles (19%), mainly due to progression of disease (54%). Eighty subjects (23%) required hospitalization, infection being the main cause (51%). Ninety-day survival was 91.8%.Conclusion. Infection is common among myeloma patients who receive daratumumab. Myeloma patients who receive daratumumab in conjunction with multidrug chemotherapy regimens have an increased risk of infection and neutropenia. Because daratumumab is given predominantly as outpatient therapy, a greater understanding of the potential immunomodulatory effects of daratumumab will lead to increased vigilance in identifying and treating clinically significant infections.

“Risk of de novo or secondary cancer after solid organ or allogeneic haematopoietic stem cell transplantation”

“…Further, fatal events were reviewed as described previously to be able to ascertain possible overlooked cancer, i.e. cancers not previously recorded (29).…”

Recipient and Center Factors Associated With Immunosuppression Practice Beyond the First Year After Liver Transplantation and Impact on Outcomes

“…Reliably establishing the underlying COD requires a systematic approach to avoid underestimating the contribution of key post-transplant complications. 40,41 These aspects should be further investigated prospectively and/or using alternate data sources to better understand the mechanisms by which immunosuppression regimens may alter post-LT outcomes.…”

Validation of cause of death classification after heart transplantation and cause‐specific life expectancy compared to the general population

“…Recently, a new method, the Classification of death causes after transplantation (CLASS) was developed in a broad transplantation context, and shown to display high reliability by Wareham et al 8 Substantial discordance was observed between the CLASS classification and death causes reported from clinical routine in the Danish National Death Cause Registry. 8 The importance of individual causes of death can be described with several metrics. One highly relevant measure is life expectancy and lifeyears lost, calculated from comparison with a normal population.…”

“…The death cause was determined according to the CLASS death cause classification. 8 Agreement was defined as the same death cause (e.g., infection) including sub group (e.g., bacterial). In the cases where the selected death cause differed between the two reviewers, a board consisting of the two reviewers and a consultant heart failure cardiologist repeated the journal review and agreed on an adjudicated death cause.…”