Lymphoma Research Foundation

7074 Background: Adverse psycho-social outcomes (APSO’s) are common side effects often underreported which have great impact on the wellbeing of patients with lymphoma or chronic lymphocytic leukemia (CLL). As patient’s traverse through their unique cancer journey, relationships with their care team yield varying degrees of confidence. We explored how confidence in both the management of their care and in the doctor coordinating their care was associated with various APSO’s. Methods: A cross-sectional, anonymous online global survey directed at patients with lymphoma or CLL was deployed in 2024. Two questions asked how confident the patient feels about 1) the management of their care (MOC) and 2) the doctor coordinating their care (DCC). Patients were split into dichotomous groups who were and were not confident. Nominal logistic regression was used to explore how answers to these two questions influenced the prevalence of 19 different APSO’s controlling for age and biological sex. Results were expressed in odds ratios with 95% confidence intervals. Results: Responses were received from 5,186 patients with 64% female and a median age of 61 [20-96]. Significantly increased incidence of APSO’s associated with a lack of confidence in the MOC included: conflicts between beliefs and cancer treatment OR = 2.3 [1.4 – 3.6]; loss of meaning/purpose OR = 1.9 [1.5 – 2.4]; depression OR = 1.7 [1.4 – 1.99]; grief/loss OR = 1.6 [1.3 – 1.96]; loss of interest in usual activities OR = 1.6 [1.3 – 1.9]; post-traumatic stress disorder OR = 1.5 [1.2 – 1.98]; isolation/loneliness OR = 1.5 [1.3 – 1.9]; feelings of worthlessness/being a burden OR = 1.5 [1.2 – 1.9]; loss of self-esteem OR 1.5 [1.2 – 1.8]; anxiety OR = 1.5 [1.2 – 1.7]; fear of incapacitation OR = 1.4 [1.1 – 1.7]; changes in relationships OR = 1.3 [1.1 – 1.6]; worry OR = 1.3 [1.1 – 1.5]. APSO’s that significantly increased due to a lack of confidence in DCC included: anger OR = 1.6 [1.2 – 2.0]; isolation/loneliness OR = 1.5 [1.2 – 1.9]; fear of incapacitation OR = 1.5 [1.1 - 1.9]. The remaining APSO’s examined failed to produce significant differences regarding patient confidence levels. This analysis illustrates that approximately 73% of the APSO’s reviewed in our survey had significant odds of being associated with patients who reported a lack of confidence in their MOC or the DCC. Conclusions: These results suggest that patients with low confidence in the management of their care plan and in the doctor coordinating their care may disproportionately experience APSO’s. It is important that care teams take time to build relationships with their patients to help reinforce confidence in their care. In doing so the patient might experience fewer APSO’s. Going forward, we plan to explore the effect of general practitioner involvement on patient confidence and the effect confidence has on physical side effects experienced by patients with lymphoma and CLL.

Aims Therapeutic advancements have significantly improved patient outcomes in blood cancers. However, racial and ethnic disparities persist in treatment and access to care. Telehealth offers a promising solution to these disparities by using electronic and telecommunication technologies to deliver healthcare remotely. Ensuring access to telehealth depends not just on the technologies, but on the broader enabling environment, especially policy harmonization, communications infrastructure, and skills. This paper aims to advocate for the expanded use of telehealth in blood cancer management, highlighting its potential to improve equity and outcomes. Materials and methods An expert forum discussion results informed this systematic literature review which was performed to better understand the applied Telehealth solutions and the expected benefits. The forum discussion and the literature review findings were aggregated and reviewed by experts and patient advocates with personal experience in blood cancer. Results Our review of the literature yielded 18 relevant papers. Studies included patients from various disease areas; some studies used broader definitions of cancer to include more patients (i.e. acute leukemias and malignant lymphomas), while others were more specific to a particular condition. The identified Telehealth solutions were classified into two groups: solutions focusing on electronic consultation (n = 10) and solutions focusing on a specific intervention to improve patients’ health status (n = 8). A larger variety of outcomes were found in these studies, including quality of life, patient and clinicians’ acceptance, adherence, costs, and resource use. Conclusions Initial findings demonstrate that telehealth can potentially improve patient outcomes for people living with blood cancer, including improved patient quality of life, increased clinician acceptance, better adherence, and reduced costs and resource use to the health system. While evidence for virtual consultations show promising results, further research is needed due to the variety of study settings evaluated in this review. Providers and health systems need additional data on the positive economic impact of Telehealth related to the diagnostic journey and access to treatment.

Several recent studies have investigated the validity of precautionary practices for lymphedema risk reduction after breast cancer treatment, such as avoidance of blood pressure measurements, skin puncture, blood draws, and use of prophylactic compression during air travel. Other studies have elucidated risk factors for breast cancer-related lymphedema, such as axillary lymph node dissection and skin infection (cellulitis). Combining the current evidence base with the consensus opinion of lymphatic experts assembled at the American Cancer Society/Lymphology Association of North America Summit in October 2023, updated evidence-based risk reduction recommendations are presented for those with or at risk of breast cancer-related lymphedema. Recommendation topics include prospective surveillance, patient education, individual risk factors, exercise, blood pressure, skin care and hygiene, skin puncture and blood draws, surgical procedures, prophylactic compression, air travel, and hot climate and sauna. These recommendations will help inform education and medical choices for individuals treated for breast cancer who are at risk of or diagnosed with breast cancer-related lymphedema. More high-quality evidence is required to allow the development of risk reduction recommendations for other cancer types such as gynecological, melanoma, and head and neck. It is recommended that clinicians and organizations serving people at risk of or with lymphedema align risk reduction guidelines with the evidence-based recommendations provided within this consensus document and companion manuscripts from the American Cancer Society/Lymphology Association of North America Lymphedema Summit: Forward Momentum: Future Steps in Lymphedema Management.

7082 Background: Cutaneous T-cell lymphoma (CTCL) is a rare form of non-hodgkin’s lymphoma. The most common type of CTCL is Mycosis Fungoides (MF) accounting for 50-60% of cases, while Sezary Syndrome, the leukemic variant of MF accounts for 2-5% of cases. Extracutaneous involvement occurs mainly in lymph nodes or blood; 25% of patients (pts) are diagnosed at advanced stage with a 5-year survival of 15-25%. KIR3DL2 is a killer immunoglobulin-like receptor, expressed in 90% of SS pts, and 50% of MF pts. Lacutamab is a first-in-class monoclonal antibody designed to specifically deplete KIR3DL2-expressing cells via antibody-dependent cell-cytotoxicity and phagocytosis. Methods: TELLOMAK is an international, open-label, multi-cohort phase 2 trial (NCT03902184). MF pts who had received at least 2 prior systemic therapies were allocated to different cohorts according to KIR3DL2 expression in skin. Lacutamab 750 mg is administered as an intravenous infusion until disease progression or unacceptable toxicity. Primary endpoint was Objective Response Rate (ORR) by global response score based on the evaluation of 4 compartments: skin, blood, lymph nodes and viscera according to International Consensus criteria (Olsen 2011; sensitivity analysis vs revised Olsen 2022). Secondary endpoints included other efficacy endpoints, safety, and quality of life. Here we report data of all MF patients, and according to KIR3DL2 status. Results: At the data cutoff of October 13, 2023, recruitment was completed, with 107 pts enrolled. Median age was 62 years. Median number of previous systemic lines was 4 (range: 1-14). Median follow-up was 11.8 months (m) (95% CI 9.9-13.8). ORR was 16.8% (CI 10.9, 25.0; Olsen 2011), and 22.4% (CI 15.6, 31.2; Olsen 2022), response in skin and blood was 29.0% (CI 21.2, 38.2) and 40.0% (CI 24.6, 57.7) respectively. Median time to response was 1.0 months and median PFS 10.2m (CI 6.5, 16.8). Among the KIR3DL2 ≥1% pts (N=48), ORR was 20.8% (CI 11.7,34.3; Olsen 2011), and 29.2% (CI 18.2, 43.2; Olsen 2022), response in skin and in blood was observed in 33.3% (CI 21.7, 47.5) and 41.2% (CI 21.6, 64.0) respectively. Median time to response was 1.0 month and median PFS was 12.0 m (CI 5.6, 20.0). Median duration of response was not reached. Grade ≥ 3 Treatment-related (TR) Treatment-Emergent Adverse events (TEAEs) were observed in 4/107 (3.7%) pts, serious TR TEAEs were observed in 4/107 (3.7%) pts and 3/107 (2.8%) pts discontinued study drug due to TR TEAEs. The most common (>10%) TR TEAEs were fatigue (11.2%), nausea (11.2%), asthenia (10.3%), and arthralgia (10.3%). Conclusions: The data from the heavily pre-treated MF population enrolled to the TELLOMAK study confirms promising clinical activity of lacutamab regardless of KIR3DL2 expression, with a favorable safety and tolerability profile. These data support the further development of lacutamab in an effort to bring improved treatments to patients with CTCL. Clinical trial information: NCT03902184 .

Simple SummaryCAR T-cell therapy became standard of care for patients with relapsed or refractory large B-cell lymphoma. However, their administration can be accompanied by toxicities, such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. It is important to identify patients at risk for these toxicities in order to start an early intervention in high-risk patients and guide outpatient CAR T-cell treatment. As a consequence, several easy-to-use risk scores including the EASIX and its derivatives were developed. However, in the available studies, disparities existed among the used endpoints and cutoff values, hampering the utility of these tools in practice. This study aims to validate these EASIX scores in a population-based cohort. This can be used to select the best predictive model and to further guide optimization of the proposed risk scores.Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) can hamper the clinical benefit of CAR T-cell therapy in patients with relapsed/refractory large B-cell lymphoma (r/r LBCL). To assess the risk of CRS and ICANS, the endothelial activation and stress index (EASIX), the modified EASIX (m-EASIX), simplified EASIX (s-EASIX), and EASIX with CRP/ferritin (EASIX-F(C)) were proposed. This study validates these scores in a consecutive population-based cohort. Patients with r/r LBCL treated with axicabtagene ciloleucel were included (n = 154). EASIX scores were calculated at baseline, before lymphodepletion (pre-LD) and at CAR T-cell infusion. The EASIX and the s-EASIX at pre-LD were significantly associated with ICANS grade ≥ 2 (both p = 0.04), and the EASIX approached statistical significance at infusion (p = 0.05). However, the predictive performance was moderate, with area under the curves of 0.61–0.62. Validation of the EASIX-FC revealed that patients in the intermediate risk group had an increased risk of ICANS grade ≥ 2 compared to low-risk patients. No significant associations between EASIX scores and CRS/ICANS grade ≥ 3 were found. The (m-/s-) EASIX can be used to assess the risk of ICANS grade ≥ 2 in patients treated with CAR T-cell therapy. However, due to the moderate performance of the scores, further optimization needs to be performed before broad implementation as a clinical tool, directing early intervention and guiding outpatient CAR T-cell treatment.

<div>Abstract<p><b>Purpose:</b> The ubiquitin-proteasome pathway has been validated as a target in non–Hodgkin's lymphoma through demonstration of the activity of the proteasome inhibitor bortezomib.</p><p><b>Experimental Design:</b> Another potentially attractive target is the human homologue of the murine double minute-2 protein, HDM-2, which serves as the major p53 E3 ubiquitin ligase; we therefore evaluated the activity of a novel agent, MI-63, which disrupts the HDM-2/p53 interaction.</p><p><b>Results:</b> Treatment of wild-type p53 mantle cell lymphoma (MCL) cell lines with MI-63 resulted in a dose- and time-dependent inhibition of proliferation, with an IC<sub>50</sub> in the 0.5 to 5.0 μmol/L range. MI-63 induced p53 and HDM-2 accumulation, as well as other downstream p53 targets such as p53 up-regulated modulator of apoptosis and p21<sup>Cip1</sup>. This was associated with cell cycle arrest at G<sub>1</sub>-S; activation of caspase-3, caspase-8, and caspase-9; cleavage of poly-(ADP-ribose) polymerase; and loss of E2F1. HDM-2 inhibition caused phosphorylation of p53 at multiple serine residues, including 15, 37, and 392, which coincided with low levels of DNA strand breaks. DNA damage occurred in a small percentage of cells and did not induce phosphorylation of the DNA damage marker H2A.X<sup>Ser139</sup>. Combinations of MI-63 with the molecularly targeted agents bortezomib and rapamycin showed synergistic, sequence-dependent antiproliferative effects. Treatment of primary MCL patient samples resulted in apoptosis and induction of p53 and p21, which was not seen in normal controls.</p><p><b>Conclusions:</b> These findings support the hypothesis that inhibition of the HDM-2/p53 interaction may be a promising approach both by itself and in combination with currently used chemotherapeutics against lymphoid malignancies.</p></div>