Disease Overview
Mantle cell lymphoma (MCL) is a non‐Hodgkin lymphoma characterized by involvement of the lymph nodes, spleen, blood and bone marrow with a short remission duration to standard ...therapies and a median overall survival (OS) of 4‐5 years.
Diagnosis
Diagnosis is based on lymph node, bone marrow, or tissue morphology of centrocytic lymphocytes, small cell type, or blastoid variant cells. A chromosomal translocation t (11:14) is the molecular hallmark of MCL, resulting in the overexpression of cyclin D1. Cyclin D1 is detected by immunohistochemistry in 98% of cases. The absence of SOX‐11 or a low Ki‐67 may correlate with a more indolent form of MCL. The differential diagnosis of MCL includes small lymphocytic lymphoma, marginal zone lymphoma, and follicular lymphoma.
Risk Stratification
The MCL International Prognostic Index (MIPI) is the prognostic model most often used and incorporates ECOG performance status, age, leukocyte count, and lactic dehydrogenase. A modification of the MIPI also adds the Ki‐67 proliferative index if available. The median OS for the low‐risk group was not reached (5‐year OS of 60%). The median OS for the intermediate risk group was 51 months and 29 months for the high risk group.
Risk‐Adapted Therapy
For selected indolent, low MIPI MCL patients, initial observation may be appropriate therapy. For younger patients with intermediate or high risk MIPI MCL, aggressive therapy with a cytotoxic
Regimen followed by autologous stem cell transplantation should be considered. Rituximab maintenance after autologous stem cell transplantation has also improved the progression‐free and overall survival. For older symptomatic MCL patients with intermediate or high risk MIPI, combination chemotherapy with R‐CHOP, R‐Bendamustine, or a clinical trial should be considered. In addition, rituximab maintenance therapy may prolong the progression‐free survival. At the time of relapse, agents directed at activated pathways in MCL cells such as bortezomib (NFkB inhibitor), lenalidamide (anti‐angiogenesis) and Ibruitinib (Bruton's Tyrosine Kinase BTK inhibitor) have demonstrated excellent clinical activity in MCL patients. Autologous or allogeneic stem cell transplantation can also be considered in young patients. Clinical trials with novel agents are always a consideration for MCL patients.
For the outcome of clinical trials to have validity, participants should represent the patients that will be using the medical products, though this is often not the case. Racial and ethnic ...minorities are underrepresented in cancer clinical trials for a variety of reasons. This is a concern because people of different ages, races, and ethnicities may react differently to medical products. The estimated extent of racial disparities in clinical trial access varies in the literature, yet recent reports-such as the FDA's 2018 Drug Trials Snapshots-indicate the presence of a remarkable imbalance. A total of 5157 patients participated in oncology trials that led to approvals of 17 new drugs. Overall, 38% of all participants were women, 68% were White, 15% were Asian, 4% were Black or African American, 4% were Hispanic, and 50% were 65 years and older.1 These proportions sharply contrast with the racial distribution in the general United States population (76.6% White, 13.4% Black or African American, 5.8% Asian, 18.1% Hispanic or Latino). Further, only 36% of the trial participants were residents in the United States, which is a reflection of the increasingly international nature of phase 3 oncology trials designed to support the worldwide marketing plans of the study sponsor. According to US Census Bureau projections, more than half of the population in the United States is expected to be other than non-Hispanic White by 2045.2 In the absence of proactive planning, corrective measures, and systematic and effective intervention, the disparity between the clinical trial population and the changing population of patients with cancer in the United States is likely to worsen in the coming decades. What can be done to reverse this trend and enhance clinical trial enrollment by minorities? Increasing minority representation in the health care professions will enhance the ability of the patients to feel more comfortable with the recommended options, including clinical trial participation. In addition, the outreach of health care opportunities to neighborhoods closer to patients' homes will allow access to those without consistent transportation. Eligibility criteria that allow for patients with more co-morbidities to enroll when possible will also increase minority enrollment as well as represent a more real-world population on the study. Another recent improvement is the congressional approval of the Clinical Treatment Act, which requires Medicaid to cover the routine clinical care costs of patients associated with participation in clinical trials. Since Medicaid serves a large portion of individuals from racial and ethnic minority groups, this legislation will remove some barriers to participation in clinical trials for this patient population. With a more representative patient population, the results of these clinical trials will have more accurate outcomes in real-world patients with the illness in question. In addition, the racial and ethnic minority groups will benefit with this increased access to clinical trials and cutting-edge health care opportunities.
Angioimmunoblastic T-cell lymphoma (AITL) is an uncommon subtype of mature peripheral T-cell lymphoma (PTCL). The history of AITL is much longer and deeper than the literature would suggest given the ...many names that have preceded it. Advanced-stage disease is common with uncharacteristic laboratory and autoimmune findings that often slow or mask the diagnosis. Significant strides in the immunohistochemical and molecular signature of AITL have brought increased ability to diagnose this uncommon type of PTCL. The 2016 World Health Organization classification of lymphoid neoplasms recently acknowledged the complexity of this diagnosis with the addition of other AITL-like subsets. AITL now resides under the umbrella of nodal T-cell lymphomas with follicular T helper phenotype. Induction strategies continue to focus on increasing complete remission rates that allow more transplant-eligible patients to proceed toward consolidative high-dose therapy and autologous stem cell rescue with improving long-term survival. There are several clinical trials in which recently approved drugs with known activity in AITL are paired with induction regimens with the hope of demonstrating long-term progression-free survival over cyclophosphamide, doxorubicin, vincristine, and prednisone. The treatment of relapsed or refractory AITL remains an unmet need. The spectrum of AITL from diagnosis to treatment is reviewed subsequently in a fashion that may one day lead to personalized treatment approaches in a many-faced disease.
During the height of the coronavirus disease 2019(COVID-19) pandemic, many health care facilities needed to focus on screening for and treating patients with known or suspected COVID-19. This ...resulted in the diversion of health care workers and resources.
In theory, this practice would allow patients to get information faster and decrease the number of phone calls from the health care providers to the patients. ...shared decision-making between health ...care providers and patients is not a new concept. Assessment of electronic health record use between US and non-US health systems.
There have been several breakthroughs in nonmalignant hematology care recently, including the 2023 FDA approvals of Casgevy and Lyfgenia for the treatment of patients with sickle cell disease.1 ...During the 65th American Society of Hematology (ASH) Annual Meeting and Exposition, results from the phase 2/3 CLIMB SCD-121 trial (NCT03745287) using exagamglogene autotemcel (exa-cel) were presented, demonstrating the utility of editing ex vivo with CRISPR-Cas9 technology of the erythroid-specific enhancer region of BCL11A.2 This resulted in increased hemoglobin F production, with 96.7% of patients with severe sickle cell disease being free from vaso-occlusive events and 100% being free from hospitalization. The results demonstrated a statistically significant improvement in progression-free survival (PFS) for the combination of ibrutinib plus venetoclax vs ibrutinib plus placebo.5 In the phase 3 Perseus trial (NCT03710603), the results from the randomized trial of daratumumab (Darzalex) plus bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (D-VRd) vs VRd alone for patients with newly diagnosed multiple myeloma who were eligible for autologous stem cell transplant were presented.6 With a median follow-up of 47.5 months, the PFS was significantly improved in the D-VRd arm at 84.3% vs 67.7% in the VRd arm. Over 75% of the patients, who had disease with which prior FDA-approved therapy had failed, demonstrated a response to axatilimab, with a median failure-free survival of 17 months.7 Several of the malignant hematology studies also demonstrated the importance of minimal residual disease–negative status in multiple myeloma, non-Hodgkin lymphoma, and acute leukemias.8 With the continued progress in understanding the diagnosis, biology, and treatments for patients with malignant and nonmalignant hematologic disorders, the future remains bright for our patients.
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