Antibody-drug conjugates for previously treated aggressive lymphomas: focus on polatuzumab vedotin.

INTRODUCTION: Antibody-drug conjugates (ADCs) are immunoconjugates and comprise a monoclonal antibody that is chemically attached to a cytotoxic drug (or payload) via a stable chemical linker. Since the approval of the first ADC in 2000, there are now nine different approved agents and over 100 ADCs in the drug-development pipeline. AREAS COVERED: This review briefly describes the ADCs approved for treatment of lymphoma and their distinguishing factors in terms of target, linker and payload. The clinical implications of the use of ADCs are also considered. Here, we focus on polatuzumab vedotin, an ADC targeted to CD79b, which is approved for the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who have received at least one (EU approval) or two (US approval) prior therapies and are not eligible for bone marrow transplantation. The characteristics of polatuzumab vedotin are discussed and clinical data are presented. The future of polatuzumab vedotin clinical development, and ADCs in general, are also considered. EXPERT OPINION: ADCs represent a significant advance in the treatment of lymphoma. Polatuzumab vedotin has shown clinical efficacy and a tolerable safety profile in both first-line and R/R DLBCL; future studies are planned to further investigate this ADC.

Outcomes of auto-SCT for lymphoma in subjects aged 70 years and over.

The safety and efficacy of auto-SCT for lymphoma in older patients is not well established, particularly in those ≥70 years old. We performed a retrospective analysis comparing 17 auto-SCT recipients ≥70 years old with 39 recipients aged 65-69 years. Hematopoietic cell transplantation comorbidity index (HCT-CI) scores were similar in both groups. Nonrelapse mortality (NRM) was increased in patients aged 70 years and older (hazard ratio (HR) 6.04, P=0.0029), and OS was decreased (HR 1.98, P=0.082). 1-year NRM was 35% in patients aged ≥70 years vs 8% in those aged 65-69 years (P=0.017). The incidence of in-hospital falls was higher in those aged ≥70 years (29 vs 8%, P=0.047). In a secondary exploratory analysis, we found that the occurrence of in-hospital falls was strongly associated with inferior OS (HR 3.36, P=0.0023) and NRM (HR 4.60, P=0.009) among all patients of aged 65 years and older. We conclude that auto-SCT is feasible in older patients but that mortality rates appear increased in those over age of 70 years. In-hospital falls were correlated with higher mortality, and prevention of falls may improve outcomes. Susceptibility to falls may indicate underlying frailty and should be explored prospectively as a means of selecting older patients for auto-SCT.

Pre-transplantation physical and mental functioning is strongly associated with self-reported recovery from stem cell transplantation.

Previous studies of quality of life (QOL) note compromised QOL after stem cell transplantation (HCT), but do not usually consider the impact of pre-transplantation deficits in QOL on post transplantation outcomes. To examine these associations, multivariate models for six self-reported QOL outcomes at 6 and 12 months were constructed, considering pre-transplantation clinical status and QOL, and subsequent clinical events. Outcomes measured overall subjective health, social functioning and agreement with statements such as 'Life has returned to normal.' Of 320 autologous and allogeneic HCT recipients who completed pre-transplantation surveys, 197 completed 6-month surveys and 175 completed 12-month surveys. Pre-transplantation overall health and mental health were independent predictors of all QOL outcomes at 6 months. Baseline physical health was also predictive of four of six outcomes at 12 months. In contrast, disease risk was predictive only of enjoying normal activities at 6 months. Relapse and chronic graft-versus-host disease were associated with poorer QOL. In conclusion, pre-transplantation self-reported physical and mental health are more strongly associated with QOL after HCT than commonly noted baseline clinical predictors such as age and disease risk. Measurement of baseline QOL can help place the effects of the transplantation procedure in context.

Nutritional and other postoperative management of neonates with short bowel syndrome correlates with clinical outcomes.

OBJECTIVE: To determine correlates of clinical outcomes in patients with short bowel syndrome (SBS). METHODS: Retrospective medical record review of neonates treated between 1986 and 1998 who met our criteria for SBS: dependence on parenteral nutrition (PN) for at least 90 days after surgical therapy for congenital or acquired intestinal diseases. RESULTS: Thirty subjects with complete data were identified; 13 (43%) had necrotizing enterocolitis, and 17 (57%)had intestinal malformations. Mean (SD) residual small bowel length was 83 (67) cm. Enteral feeding with breastmilk (r = -0.821) or an amino acid-based formula (r = -0.793) was associated with a shorter duration of PN, as were longer residual small bowel length (r = -0.475) and percentage of calories received enterally at 6 weeks after surgery(r = -0.527). Shorter time without diverting ileostomy or colostomy (r = 0.400), enteral feeding with a protein hydrolysate formula (r = -0.476), and percentage of calories received enterally at 6 weeks after surgery (r = -0.504) were associated with a lower peak direct bilirubin concentration. Presence of an intact ileocecal valve and frequency of catheter-related infections were not significantly correlated with duration of PN. In multivariate analysis, only residual small bowel length was a significant independent predictor of duration of PN, and only less time with a diverting ostomy was an independent predictor of peak direct bilirubin concentration. CONCLUSIONS: Although residual small bowel length remains an important predictor of duration of PN use in infants with SBS, other factors, such as use of breast milk or amino acid-based formula, may also play a role in intestinal adaptation. In addition, prompt restoration of intestinal continuity is associated with lowered risk of cholestatic liver disease. Early enteral feeding after surgery is associated both with reduced duration of PN and less cholestasis.