Ajay Major

University of Colorado | UCD · Division of Hematology

The PI3K/Akt/mTOR (PAM) axis is constitutively activated in multiple lymphoma subtypes and is a promising therapeutic target. The mTOR inhibitor temsirolimus (TEM) and the immunomodulatory agent lenalidomide (LEN) have overlapping effects within the PAM axis with synergistic potential. This multicenter phase I/II study evaluated combination therapy...

Peripheral neuropathy is a common treatment-emergent side effect during the treatment of newly-diagnosed multiple myeloma. Although bortezomib is most commonly implicated, real-world data suggest that lenalidomide and dexamethasone (VRd) and autologous stem cell transplantation (ASCT) may also contribute to neuropathy and health-related quality of...

There are limited data describing the impact of active surveillance on longitudinal health-related quality of life (HRQoL) in patients with indolent non-Hodgkin lymphomas (NHL). A cohort of untreated indolent NHL patients completed FACT-LYM questionnaires at 6, 12, 18, 24, and 36 months after diagnosis. Longitudinal FACT-LYM scores were analyzed by...

Checkpoint inhibitor (CPI) therapy with anti-PD-1 antibodies has been associated with mixed outcomes in small cohorts of aggressive B-cell lymphoma patients following CAR T-cell therapy failure. To more definitively define CPI therapy efficacy in this population, we retrospectively evaluated clinical outcomes in a large cohort of 96 patients with a...

There has been a rapid expansion of novel therapeutics for hematologic malignancies, including monoclonal antibodies, small molecules, and cellular therapies, which confer different treatment-related toxicities and symptomatic adverse events (AEs) than traditional cytotoxic chemotherapies. Given that patients with blood cancers are living longer wi...

Background: Bispecific antibodies (BsAbs), such as glofitamab (Glofit) and epcoritamab (Epcor), are approved treatment (tx) options for patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after ≥2 lines of therapy. While early data suggest similar efficacy and safety, frequency of administration and associated health...

Background: Indolent non-Hodgkin lymphomas (iNHL) are incurable and disproportionately affect adults age >65 in whom frailty and functional impairment can impact disease management. The Vulnerable Elders Survey (VES-13) is a 13-item screening tool that incorporates age, self-rated health, physical function limitations, and functional disabilities t...

Introduction Oral oncolytic therapies (OOT) have transformed the treatment of CLL, but high costs may cause significant financial toxicity (FT) which can adversely impact patients (pts) beyond direct out of pocket costs. Associations of FT with health-related quality of life (HRQoL) and medication adherence is unknown for OOT in CLL. We performed a...

Background Patient-reported outcomes (PRO) measures are used in lymphoma clinical trials to assess health-related quality of life (QoL) and tolerability of novel treatment regimens, including CAR T-cell and bispecific antibody therapies. However, outcomes in the clinical trial setting often differ from those in real-world patient cohorts. The Blood...

Introduction: The effect of TP53 alterations on response to therapy is poorly understood in LBCL, with previous studies demonstrating worse overall survival (OS) for LBCL patients (pts) with TP53 aberrations. However, these studies pre-dated novel therapies, including chimeric antigen receptor T-cell therapy (CAR T), bispecific antibody (BsAb), and...

Background: Polatuzumab vedotin (Pola) is an antibody drug conjugate targeting CD79b that incorporates the microtubule disrupting monomethyl auristatin E payload. Pola was approved in 2023 for the upfront treatment of diffuse large B cell lymphoma (DLBCL) in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (polaRCHP) based...

Introduction: Bispecific antibodies (BsAbs) epcoritamab (Epco) and glofitamab (Glofit) are approved in the US for the treatment of patients (pts) with relapsed or refractory (r/r) large B-cell lymphomas (LBCLs) based upon high response rates and manageable toxicity profiles reported in pivotal trials. However, data on outcomes for pts treated with...

MRD2STOP is a pragmatic trial evaluating maintenance therapy cessation guided by measurable residual disease (MRD) negativity in multiple myeloma (MM). Eligible patients had previous MRD < 10⁻⁵, received ≥1 year of maintenance, and were prospectively confirmed to have undetectable disease by positron emission tomography, bone marrow (BM) flow cytom...

Short diagnosis-to-treatment interval (DTI) is associated with high-risk disease and poor survival in diffuse large B-cell lymphoma (DLBCL). There is a paucity of literature on DTI and survival in DLBCL treated with first-line DA-R-EPOCH. We hypothesized that rapid initiation of DA-R-EPOCH in aggressive and high-risk DLBCL mitigates the adverse pro...

106 Background: Measurable residual disease (MRD) negativity is a potential marker for the absence of disease in multiple myeloma (MM), which could be used to guide treatment cessation. MRD2STOP (NCT04108624) is a prospective study investigating outcomes among patients with sustained multimodal MRD negativity who discontinue maintenance therapy. Me...

e23157 Background: While oral oncolytics have transformed CLL treatment, high costs may cause significant FT adversely impacting patients beyond direct out-of-pocket (OOP) costs. The association of FT with QoL and medication adherence has not been characterized with oral oncolytics in CLL. Methods: Electronic PRO surveys were longitudinally adminis...

9005 Background: Clinical investigator training (CIT) is commonly performed in an apprenticeship manner rather than following a prospective education model. This may lead to disparities in educational prospects. There is greater accesiblity for training opportunites prevailing in larger academic institutions – an advantage not always within reach f...

We evaluated the efficacy and safety of 24 cycles of Dara in combination with carfilzomib (K), lenalidomide (R), and dexamethasone (d) without autologous stem cell transplant (ASCT) in newly diagnosed multiple myeloma (NDMM) irrespective of ASCT eligibility in a single-arm, phase II study. The primary endpoint was the rate of stringent complete res...

Little is known about risk factors for central nervous system (CNS) relapse in mature T- and NK-cell neoplasms (MTNKN). We aimed to describe the clinical epidemiology of CNS relapse in patients with MTNKN and developed the CNS relapse In T-cell lymphoma Index (CITI) to predict patients at highest risk of CNS relapse. We reviewed data from 135 patie...

The 65th American Society of Hematology (ASH) Annual Meeting was held from December 9 to 12, 2023, in San Diego, California, and online. This year's Friday Scientific Workshop on Hematology and Aging was focused on investigating clinical markers and scores that help assess biological rather than chronological aging. Herein, we summarize select oral...

PURPOSE Nodular lymphocyte–predominant Hodgkin lymphoma (NLPHL) is a rare cancer, and large international cooperative efforts are needed to evaluate the significance of clinical risk factors and immunoarchitectural patterns (IAPs) for all stages of pediatric and adult patients with NLPHL. METHODS Thirty-eight institutions participated in the Globa...

Hospice is underutilized by patients with hematologic malignancies (HM), and when patients are referred, they are typically more ill, hospitalized, and with shorter length of stay (LOS) than patients with solid tumors (ST), limiting research about home hospice care experiences of patients with HM. In this mixed-methods study, we examined the hospic...

Except for anaplastic large cell lymphoma, five-year progression free survival (PFS) for peripheral T-cell lymphomas (PTCLs) with anthracycline-based chemotherapy is ~25%. Dose adjusted (DA)-EPOCH (etoposide, prednisone, vincristine, doxorubicin, and cyclophosphamide) is an anthracycline based regimen for PTCLs. The programmed death (PD) pathway is...

Venetoclax with azacitidine (ven/aza) is a lower-intensity therapeutic regimen that has been shown to improve outcomes in elderly patients with acute myeloid leukemia (AML). Measurable residual disease (MRD) using flow cytometry is a valuable tool for the prediction of relapse in AML using conventional therapies and ven/aza; however, the prognostic...

Patients with relapsed and refractory (R/R) aggressive B-cell non-Hodgkin lymphomas have historically poor survival outcomes, with chimeric antigen receptor T-cell (CAR-T) therapy now presenting a curative option for a subset of those patients. However, with the approval of several novel bispecific monoclonal antibody (BsAb) therapies with consider...

Background: Understanding the symptoms and quality of life (QOL) over time of adults with follicular lymphoma (FL) is important for treatment decision-making and clinical management. However, there are limited population-level data on the long-term QOL of adults with FL. We aim to describe the real-world, long-term QOL of adults with newly diagnose...

Background: Patients (pts) with classical Hodgkin Lymphoma (cHL) who become refractory to both BV and anti-PD-1 therapies (double refractory, DR) or intolerant (INT) of BV and anti-PD-1 therapies have limited treatment options. There is limited information regarding optimal treatment approaches in these pts. Rechallenging with BV or anti-PD-1 thera...

Background: Assaying for minimal residual disease (MRD) in the peripheral blood (PB) of patients with multiple myeloma (MM) could solve issues of patchy and extramedullary disease leading to false-negative MRD tests based on bone marrow (BM) only assessments. However, PB testing is challenging due to limited circulating myeloma cells and/or parapro...

Background Chimeric antigen receptor T-cell therapies (CAR-T) significantly improve survival and health-related quality of life (HRQoL) in clinical trials of relapsed hematologic malignancies. However, the impact of CAR-T on real-world longitudinal patient-reported outcomes (PROs), particularly in the immediate post-CAR-T period during which patien...

Introduction: A previous trial showed that Dara-KRd for 8 cycles without ASCT led to a minimal residual disease (MRD) negativity rate of 71% at 10 -5 in NDMM (Landgren et al. JAMA Oncology 2021). MRD-adapted Dara-KRd with ASCT led to an MRD(-) rate of 71% at 10 -6 with a 3-year progression-free survival (PFS) of 88%, 79%, and 50% in pts with 0, 1 o...

Background: Brentuximab vedotin (BV) and anti-PD-1 therapies (nivolumab and pembrolizumab) have changed the therapeutic landscape for patients (pts) with classical Hodgkin lymphoma (cHL) over the past decade. Although first proven to be beneficial in relapsed and refractory cHL, these therapies have moved earlier in the treatment algorithm given su...

Background: Data on the clinical activity of venetoclax (ven) in lymphoplasmacytic lymphoma (LPL) are primarily limited to a phase 2 trial of ven monotherapy for a 2-year duration in 32 patients (pts) with relapsed/refractory IgM LPL who received a median of 2 prior treatments (tx), including 16 pts with prior BTK inhibitors (BTKi) (Castillo et al,...

This chapter includes answers to practice-based questions with case studies covering the new principles of diagnosis, staging, treatment, and outcomes in Chronic Lymphocytic Leukemia (CLL). In the past several years, there has been a shift in the CLL treatment paradigm toward greater utilization of targeted agents over traditional chemoimmunotherap...

Measurable residual disease (MRD) is the most important post-treatment predictor of relapse in acute myeloid leukemia (AML). However, molecular MRD is less well validated than flow MRD with respect to prognostic import, particularly after low-intensity therapies like venetoclax/azacitidine (ven/aza). To test the hypothesis that multi-gene molecular...

A 56-year-old woman presented to the emergency department (ED) with 5 days of right lower quadrant abdominal pain, flank pain, and urinary retention. Her review of systems was negative for hematuria, vaginal bleeding, vaginal discharge, vomiting, and diarrhea. Her past medical history was notable for chronic obstructive pulmonary disease on 3 L/min...

Background: Carfilzomib (CFZ) is a second-generation proteasome inhibitor with activity in multiple myeloma (MM) that is associated with cardiotoxicity and dyspnea. The pathophysiology and risk factors for developing these toxicities are not well described. We are conducting a prospective observational study (NCT04827563) of longitudinal changes in...

As first-year medical students at Albany Medical College, authors Aleena Paul and Ajay Major founded in-Training, an online peer-reviewed publication by and for medical students, in 2012. Since their launch, in-Training has published over 2,000 works by medical students across the globe, from narrative medicine reflections to poetry to op-eds to po...

Multiple myeloma (MM) is a cancer of older adults and those who are more frail are at high risk of poor outcomes. Current tools for identifying and categorizing frail patients are often static and measured only at the time of diagnosis. The concept of dynamic frailty (i.e. frailty changing over time) is largely unexplored in MM. In our study, adult...

There is a paucity of large‐scale data delineating outcomes and prognostication of older patients with primary central nervous system lymphoma (PCNSL). We retrospectively analyzed 539 newly‐diagnosed PCNSL patients ages ≥60 years across 20 U.S. academic centers. The median age was 70 years (range 60–88); at least one geriatric syndrome was present...

The objective of this multicenter retrospective study was to examine the incidence, patient characteristics, pathology, and outcomes associated with Epstein-Barr virus (EBV)-related CNS lymphoma (CNSL) in older patients. Among 309 CNSL patients aged ≥60, 11.7% had EBV + tumors of which 72.2% were solid organ transplant (SOT)-related post-transplant...

Simple Summary Extranodal NK/T-cell lymphoma (ENKTL) is an aggressive blood cancer with poor survival rates, particularly for patients with advanced-stage and relapsed disease. Emerging research on the genetic and molecular causes of ENKTL have revealed new potential treatment strategies. In this review, we summarize how research on the biological...

We performed a phase I study of weekly selinexor, carfilzomib, and dexamethasone (wSKd) in patients with relapsed/refractory multiple myeloma (MM). The primary objective was to identify the maximum tolerated dose (MTD) of wSKd. Secondary endpoints included overall response rate (ORR), progression‐free survival (PFS), and overall survival (OS). Prio...

We conducted a phase 1/2 study of carfilzomib, pomalidomide, and dexamethasone (KPd) followed by another cohort of KPd with daratumumab (Dara-KPd) in relapsed/refractory multiple myeloma. The primary endpoints were identification of a maximum tolerated dose (MTD) of KPd for phase 1, and rates of overall response (ORR) and near complete response (nC...

Background: Lenalidomide is a cornerstone of maintenance therapy in patients with newly diagnosed multiple myeloma after autologous stem-cell transplantation. We aimed to compare the efficacy and safety of maintenance therapy with carfilzomib, lenalidomide, and dexamethasone versus lenalidomide alone in this patient population. Methods: This stu...

Chimeric antigen receptor T-cell therapy (CAR-T) is effective against relapsed and refractory B-cell lymphomas, although durable remissions are achieved in only 30-40% of patients. One proposed mechanism of CAR-T resistance is T-cell exhaustion, mediated in part by upregulation of PD-1 and PD-L1 checkpoint proteins in the lymphoma environment. As s...

Measurable residual disease (MRD) is the most important post-treatment predictor of relapse in acute myeloid leukemia (AML) [PMID 33030517]. The bulk of clinical MRD studies in AML have been performed via multi-parameter flow cytometry and no molecular MRD platform is established for clinical use in AML. Droplet digital PCR (ddPCR) has been identif...

Central nervous system (CNS) relapse (CNSr) in patients with aggressive non-Hodgkin lymphoma is uncommon but carries a high morbidity and mortality. Data in T- and NK-cell lymphomas (TCL) are sparse, though the few small case series describing CNSr in TCL report an incidence up to 9% with median overall survival (mOS) less than 3 months (mo). We pr...

Multiple myeloma (MM) is a cancer of older adults with significant morbidity and mortality. Frail patients are a high-risk subgroup at risk for poor outcomes. While a number of tools have been developed for frailty assessment, many are measured only at baseline and do not take into account changes in frailty over time. Understanding both improvemen...

Carfilzomib (CFZ) is a second-generation proteasome inhibitor with activity in multiple myeloma (MM) that is associated with cardiotoxicity and dyspnea. The pathophysiology and risk factors for developing these toxicities, and their effect on health-related quality of life (HRQoL), are unknown. We are conducting a prospective observational study (N...

Narrative analysis, creative writing, and interactive reflective writing have been identified as valuable for professional identity formation and resilience among medical and premedical students alike. This study proposes that medical student blogs are novel pedagogical tools for fostering peer-to-peer learning in academic medicine and are currentl...

Context: Relapses involving the central nervous system (CNS) are uncommon among patients with diffuse large B-cell lymphoma (DLBCL) but carry very poor prognosis. Prophylaxis is heterogeneously prescribed around the time of frontline therapy, with no clear standard of care in terms of recipient selection or route of administration. Design: We re...

Importance: Treatment of newly diagnosed multiple myeloma (NDMM) with a quadruplet regimen consisting of a monoclonal antibody, proteasome inhibitor, immunomodulatory imide, and corticosteroid has been associated with improved progression-free survival (PFS) compared with triplet regimens. The optimal quadruplet combination, and whether this obvia...

Measurable residual disease (MRD) as assessed by next generation sequencing (NGS) using bone marrow (BM) aspirate carries prognostic significance in multiple myeloma (MM). Though its analytical sensitivity reaches 10-6, MRD assessed from BM may be vulnerable to false negatives due to patchy or extramedullary disease, or due to inadequate aspirate s...

In the POLARIX trial, pola‐R‐CHP demonstrated improved progression‐free survival (PFS) compared to R‐CHOP in untreated intermediate‐ to high‐risk DLBCL. We surveyed practicing clinicians regarding their interpretation of POLARIX, including impressions of efficacy, safety, and cost. Of 174 respondents, most from academic centers (82%) in the United...

Treatment following autologous stem cell transplantation (ASCT) for multiple myeloma (MM) remains an area of active investigation. We have shown that extended post-ASCT treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) after KRd induction improved the depth and duration of response (Jasielec et al, Blood 2020), suggesting a benefit...

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma (HL) in both children and adults. In contrast to classic HL, NLPHL nearly always expresses CD20, has a mostly indolent clinical course with high overall survival despite frequent relapses, and may undergo aggressive transformation. To build a framework for...

Rare cases of COVID‐19 vaccinated individuals develop anti‐platelet factor 4 (PF4) antibodies that cause thrombocytopenia and thrombotic complications, a syndrome referred to as vaccine‐induced immune thrombotic thrombocytopenia (VITT). Currently, information on the characteristics and persistence of anti‐PF4 antibodies that cause VITT after Ad26.C...

PURPOSE The global pediatric oncology clinical research landscape, particularly in Central and South America, Africa, and Asia, which bear the highest burden of global childhood cancer cases, is less characterized in the literature. Review of how existing pediatric cancer clinical trial groups internationally have been formed and how their research...

A 65-year-old man without past medical history presented with two weeks of progressive weakness and lethargy, edema, and short-term memory difficulties. Review of systems revealed a 40-pound unintentional weight loss over the previous six months.

Purpose: The COVID-19 pandemic led to unprecedented challenges in medical training, and we sought to assess the specific impact of COVID-19 on hematology-oncology (HO) fellowship programs. Methods: We conducted a cross-sectional anonymous online survey of 103 HO program directors (PDs) in conjunction with the American Society of Hematology (ASH)...

Purpose: Graduate medical and research training has drastically changed during the COVID-19 pandemic, with widespread implementation of virtual learning, redeployment from core rotations to the care of patients with COVID-19, and significant emotional and physical stressors. The specific experience of hematology-oncology (HO) fellows during the CO...

Purpose: There is a need for an improved understanding of clinical and biologic risk factors in pediatric cancer to improve patient outcomes. Machine learning (ML) represents the application of computational inference from advanced statistical methods that can be applied to increasing amount of data available for study in pediatric oncology. The g...

Narrative analysis, creative writing, and interactive reflective writing have been identified as valuable for professional identity formation and resilience among medical and premedical students alike. This study proposes that medical student blogs are novel pedagogical tools for fostering peer-to-peer learning in academic medicine and are currentl...

The emerging molecular and prognostic characterization of diffuse large B-cell lymphoma (DLBCL) has challenged the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treatment paradigm in recent years, with the identification of several DLBCL subtypes associated with significantly inferior survival after standard R-CHOP...

Background Rituximab induction (RI) and bendamustine-rituximab (BR) induction are both options for the frontline management of indolent non-Hodgkin lymphomas (NHLs). Although BR induces longer progression-free survival than RI, BR confers more toxicity and a longer duration of initial induction than RI. The effects of RI versus BR on health-related...

Introduction: The combination of carfilzomib, lenalidomide, and dexamethasone (KRd), with and without autologous stem cell transplantation (ASCT) is an effective regimen for newly diagnosed multiple myeloma (NDMM) (Jakubowiak et al., Blood 2012 and Jasielec et al., Blood 2020). The addition of daratumumab to KRd (Dara-KRd) for 8 cycles led to a mea...

Background Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma that typically presents with early-stage favorable disease and exhibits an indolent clinical course with long-term remissions and eventual relapse. Histopathologic variants of NLPHL have recently been described and may have poorer outcomes compa...

Treatment of older patients (pts) with PCNSL is challenging due to the prevalence of comorbidities, frailty, and complexities with effective delivery of chemotherapy (CT). Optimal induction CT or consolidation for older PCNSL pts are unknown. Moreover, there are a paucity of large-scale prognostication studies available. We analyzed post-induction...

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a newly described hematologic disorder, which presents as acute thrombocytopenia and thrombosis after administration of the ChAdOx1 nCov-19 (AstraZeneca) and Ad26.COV2.S (Johnson & Johnson) adenovirus-based vaccines against COVID-19. Due to positive assays for antibodies against platelet...

Prophylaxis is commonly used to prevent central nervous system (CNS) relapse in diffuse large B cell lymphoma, with no clear standard of care. We retrospectively evaluated 1162 adult patients across 21 US academic centers with DLBCL or similar histologies who received single-route CNS prophylaxis as part of frontline therapy between 2013-2019. Prop...

Treatment of older patients (pts) with PCNSL is challenging due to the prevalence of comorbidities, frailty, and effective delivery of chemotherapy (CT). Optimal induction CT or consolidation for older PCNSL pts are unknown. Moreover, there are a paucity of large-scale prognostication studies available. We analyzed post-induction treatment patterns...

Treatment of older patients (pts) with PCNSL is challenging due to the prevalence of comorbidities, frailty, and effective delivery of chemotherapy (CT). Optimal induction CT and consolidation for older PCNSL pts are unknown. Moreover, there are a paucity of large-scale prognostication studies available. We analyzed post-induction treatment pattern...

Oncology health-care workers (HCWs) are facing substantial stressors during the current coronavirus disease 2019 (COVID-19) pandemic, resulting in a wide range of acute stress responses. To appropriately meet the growing mental health needs of HCWs, it is imperative to differentiate expectable stress responses from post-traumatic stress disorder an...

We present the following illustrative case of a patient with relapsed B-ALL who developed HLH/MAS after treatment with a commercial CAR-T product and was successfully managed with anakinra, interleukin-6 (IL-6) inhibitors, and corticosteroids. Our case highlights several key challenges surrounding the presentation, diagnosis, and management of CAR-...

Problem: There are significant barriers for resident physicians seeking mental health care, including lack of time, cost, and concerns about confidentiality. The authors sought to improve access to mental health resources by addressing these barriers through the development of a confidential opt-out mental health pilot program for interns, and to a...

Background: The ongoing COVID-19 pandemic has profoundly affected the mental health of health care workers (HCWs), and optimal strategies to provide psychological support for HCWs are not currently established. Aims: To rapidly review recently-published literature on the mental health of HCWs during the COVID-19 pandemic. Methods: Query of all quan...