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Presenter : Andrew D. Zelenetz

CAR T cells have demonstrated activity in relapsed/refractory non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL), indolent non-Hodgkin lymphoma, and mantle cell lymphoma. For patients with chemorefractory disease, CAR T cells can provide a durable complete response in a portion of patients, which represents a major advance in the field. For patients with chemosensitive disease, however, additional data are needed to determine whether CAR T cells are preferable to conventional approaches. Studies in DLBCL have shown that patients experiencing a PET-positive partial response after second-line chemotherapy have long-term outcomes after high-dose therapy and autologous stem cell rescue that are similar to CAR T-cell therapy, with decreased toxicity and cost. Alternative third-line options such as tafasitamab/lenalidomide and bispecific antibodies may also have a role for patients with chemorefractory disease.

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Presenter : Natalie S. Callander

Smoldering multiple myeloma represents approximately 10% to 15% of all myeloma cases, but more thorough evaluation may decrease that number in the future. Risk stratification is important in this patient population to avoid overtreatment or undertreatment. Patients with low-risk disease can be observed without treatment, but those at higher-risk should be enrolled on clinical trials. If a clinical trial is not an option in these patients, a time-limited intervention with lenalidomide ± dexamethasone can be considered.

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Presenter : William G. Wierda

Progress in the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma has led to a renewed focus on minimal residual disease as a treatment endpoint, particularly in assessing survival outcomes with combination therapies. B-cell receptor signaling pathway inhibitor monotherapy is associated with low rates of undetectable minimal residual disease, and continued treatment is still required; however, BCL-2 inhibitor therapy with venetoclax is associated with high rates of undetectable minimal residual disease, as are new combinations with BCL-2 inhibitors. Early research indicates that BCL-2 inhibitors may be an effective treatment option for disease that is refractory to Bruton’s tyrosine kinase (BTK) inhibitor therapy.

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Luciano J. Costa and Saad Z. Usmani

Multiple myeloma is a very heterogeneous disease. Despite advances in diagnostics and therapeutics, a subset of patients still experiences abbreviated responses to therapy, frequent relapses, and short survival and is considered to have high-risk multiple myeloma (HRMM). Stage III diagnosis according to the International Staging System; the presence of del(17p), t(4;14), or t(14;16) by fluorescence in situ hybridization; certain gene expression patterns; high serum lactic dehydrogenase level; and the presence of extramedullary disease at diagnosis are all considered indicators of HRMM. More recent evidence shows that patients who experience response to therapy but with a high burden of measurable residual disease or persistence of abnormal FDG uptake on PET/CT scan after initial therapy also have unfavorable outcomes, shaping the concept of dynamic risk assessment. Triplet therapy with proteasome inhibitors, immunomodulatory agents, and corticosteroids and autologous hematopoietic cell transplantation remain the pillars of HRMM therapy. Recent evidence indicates a benefit of immunotherapy with anti-CD38 monoclonal antibodies in HRMM. Future trials will inform the impact of novel immunotherapeutic approaches, including T-cell engagers, CAR T cells, and nonimmunotherapeutic approaches in HRMM. Those agents are likely to be deployed early in the disease course in the setting of risk- and response-adapted trials.

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Timothy M. Schmidt and Natalie S. Callander

The presence of monoclonal proteins is common, with a prevalence in the United States around 5% that increases with age. Although most patients are asymptomatic, most cases are caused by a clonal plasma cell disorder. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic precursor conditions with variable risk of progression to multiple myeloma. In recent years, significant progress has been made to better understand the factors that lead to the development of symptoms and progression to myeloma. This review summarizes the current diagnosis treatment guidelines for MGUS and SMM and highlights recent advances that underscore a shifting paradigm in the evaluation and management of plasma cell precursor conditions.

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Fur-Hsing Wen, Chen Hsiu Chen, Wen-Chi Chou, Jen-Shi Chen, Wen-Cheng Chang, Chia-Hsun Hsieh and Siew Tzuh Tang

Background: Issuing do-not-resuscitate (DNR) orders has seldom been an outcome in randomized clinical trials of advance care planning (ACP) interventions. The aim of this study was to examine whether an ACP intervention facilitating accurate prognostic awareness (PA) for patients with advanced cancer was associated with earlier use of DNR orders. Patients and Methods: Participants (n=460) were randomly assigned 1:1 to the experimental and control arms, with 392 deceased participants constituting the final sample of this secondary analysis study. Participants in the intervention and control arms had each received an intervention tailored to their readiness for ACP/prognostic information and symptom-management education, respectively. Effectiveness in promoting a DNR order by facilitating accurate PA was determined by intention-to-treat analysis using multivariate logistic regression with hierarchical linear modeling. Results: At enrollment in the ACP intervention and before death, 9 (4.6%) and 8 (4.1%) participants and 168 (85.7%) and 164 (83.7%) participants in the experimental and control arms, respectively, had issued a DNR order, without significant between-arm differences. However, participants in the experimental arm with accurate PA were significantly more likely than participants in the control arm without accurate PA to have issued a DNR order before death (adjusted odds ratio, 2.264; 95% CI, 1.036–4.951; P=.041). Specifically, participants in the experimental arm who first reported accurate PA 31 to 90 days before death were significantly more likely than their counterparts in the control arm who reported accurate PA to have issued a DNR order in the next wave of assessment (adjusted odds ratio, 13.365; 95% CI, 1.989–89.786; P=.008). Both arms issued DNR orders close to death (median, 5–6 days before death). Conclusions: Our ACP intervention did not promote the overall presence of a DNR order. However, our intervention facilitated the issuance of NDR orders before death among patients with accurate PA, especially those who reported accurate PA 31 to 90 days before death, but it did not facilitate the issuance of DNR orders earlier than their counterparts in the control arm.

ClinicalTrial.gov Identification: NCT01912846

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Amy A. Kirkham, Karen A. Gelmon, Cheri L. Van Patten, Kelcey A. Bland, Holly Wollmann, Donald C. McKenzie, Taryne Landry and Kristin L. Campbell

Background: Available preliminary evidence is conflicting on whether exercise can positively influence antineoplastic treatment tolerance and in turn improve survival. Patients and Methods: This study compared chemotherapy treatment tolerance and survival among women receiving adjuvant chemotherapy for early-stage breast cancer who participated in a single-arm trial of supervised aerobic and resistance exercise programming versus a historical cohort that did not receive structured exercise programming. Results: The exercise group (EX; n=73) and control group (CTR; n=85) participants were matched on age and treatment and balanced on medical history, cancer diagnosis, and body mass index. Attendance in the EX group was 64% ± 27% of 3 offered sessions per week. For all chemotherapy agents combined, the relative risk (RR) of a chemotherapy dose reduction (RR, 0.78; 95% CI, 0.54–1.11) or delay (RR, 1.05; 95% CI, 0.62–1.80) did not differ between groups. However, the EX group had reduced relative and absolute risks of a dose reduction in doxorubicin by 60% and 18%, respectively. For all agents combined, there were no differences between groups in risk of anemia, neutropenia, or weight gain. In the EX group, dose reductions due to neutropenia (P=.027), other infections (P=.049), and fatigue (P=.037) were less common, whereas mucositis was more common (P=.023), compared with the CTR group. The EX group had reduced relative and absolute risks of weight gain on the docetaxel + cyclophosphamide regimen by 38% and 30%, respectively. After a median follow-up of 70 months (range, 54–84 months), there was no difference between the EX and CTR groups in disease-free survival events (n=8 [11%] vs n=9 [11%], respectively; log-rank test, P=.78) or overall survival events (n=5 [7%] vs n=6 [7%], respectively; log-rank test, P=.974). Conclusions: Overall, exercise programming during adjuvant chemotherapy does not appear to impact treatment tolerance or survival in women receiving common modern regimens of adjuvant chemotherapy for early-stage breast cancer. However, exercise may provide selective benefits, depending on the treatment regimen received.