Mike Cusnir

Background/Objectives: Diffuse large B-cell lymphoma (DLBCL) and high-grade follicular lymphoma (FL) are aggressive B-cell malignancies predominantly affecting older adults. R-CHOP remains the frontline standard of care, with frail and elderly patients requiring attenuated regimens such as R-mini-CHOP. Real-world comparative data in elderly and Hispanic populations remain limited. We aimed to evaluate outcomes of R-mini-CHOP versus R-CHOP in elderly patients and to explore potential differences by ethnicity. Methods: Single-center retrospective analysis of adult patients older than 70 years with DLBCL and high-grade FL, treated between January 2014 and June 2025. Clinical characteristics, treatment responses, and survival outcomes were analyzed. The overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan–Meier method. Results: A total of 136 patients were included (72 R-mini-CHOP; 64 R-CHOP). Patients receiving R-mini-CHOP were older (median 82 vs. 74 years) and had higher-risk features. Overall response rates were 88.7% and 92.6% in the R-mini-CHOP and R-CHOP groups, respectively. Two-year OS was 79.3% for R-mini-CHOP and 76.7% for R-CHOP. Median OS and PFS were not reached in either group. Elevated lactate dehydrogenase (LDH) was associated with an inferior response. We identified a trend toward better response with R-CHOP in Hispanic patients, although this was not statistically significant. Conclusions: In this real-world cohort, R-mini-CHOP achieved response and survival outcomes comparable to R-CHOP despite worse baseline characteristics. These findings support the use of dose-attenuated therapy in frail and elderly patients and suggest that equitable access to care may mitigate ethnic disparities in outcomes.

Background A clinical protocol was designed to incorporate multiple spatial and temporal immunomodulatory cascades using the properties of living, allogeneic, activated memory Th1 cells (“AlloStim®) with the aim to determine if the immunotherapy would elicit a survival signal in an immunotherapy-refractory cold tumor indication. Metastatic colorectal cancer (CRC) patients that present with microsatellite stable (MSS)/proficient mis-match repair (pMMR) genotype “cold” tumors are resistant to immunotherapy. Methods To test this hypothesis, this immunotherapy was evaluated in a Phase IIB single arm, multi-center clinical trial in third-line MSS/pMMR metastatic CRC patients with overall survival (OS) as the primary end-point. Third-line CRC patients historically have a limited median OS of only around 5 months on placebo. AlloStim® was administered weekly in intradermal and intravenous doses in 3-five-week cycles, followed by optional monthly intravenous booster infusions. Results 29 third-line MSS/pMMR immunotherapy-refractory metastatic CRC patients were recruited from 4 cancer centers in the USA. The median OS was 16.4 months (95% CI: 8.6-18mo) with a 60% survival at 12 months and 39% survival at 18 months, which compares favorably to historical randomized, controlled trial data of active drugs in this indication. The therapy was well tolerated with only mild treatment-related adverse events. Conclusion AlloStim® immunotherapy demonstrated a strong survival signal in immunotherapy-refractory third-line metastatic MSS/pMMR CRC compared to historical controls providing a proof-of-concept for the protocol design and providing evidence of potential anti-tumor activity despite significant radiological progression. These findings support advancement to well-designed, prospective, randomized-controlled clinical studies powered to confirm the potential survival signal.

Patients with advanced melanoma resistant to immune checkpoint or BRAF/MEK inhibitors have treatment options with relatively low efficacy. Lifileucel, a one-time autologous tumor-infiltrating lymphocyte cell therapy, was approved in the United States on the basis of the pivotal C-144-01 study. A 5-year follow-up of the C-144-01 trial assessed the long-term efficacy and safety of lifileucel. At the cutoff date (November 20, 2024), the objective response rate was 31.4% (complete response [CR], 5.9%; partial response [PR], 25.5%). Overall, 79.3% of patients had tumor burden reduction; 16 had deepened responses with four converting from PR to CR > 1 year after lifileucel infusion; 31.3% of responders completed the 5-year assessment with ongoing responses. The median duration of response was 36.5 months. Responders (n = 48) had lower tumor burden and fewer liver or brain metastases than the overall population. The median overall survival (OS) was 13.9 months, with a 5-year OS of 19.7%. Adverse events were consistent with nonmyeloablative lymphodepletion and interleukin-2 safety profiles and declined rapidly within 2 weeks after lifileucel infusion. Most grade 3/4 cytopenias resolved to grade ≤2 by day 30. This 5-year analysis demonstrated long-term benefit and meaningful OS with one-time lifileucel therapy, with no additional long-term safety concerns.

Third-line metastatic colorectal cancer (CRC) is refractory to chemotherapy and the available third-line therapies have limited efficacy with significant toxicities. Approximately 95% of metastatic CRC patients present with microsatellite stable (MSS)/proficient mis-match repair (pMMR) genotype that are resistant to immunotherapy. Therefore, there remains a high unmet need for new treatment options for these patients. Background/Objectives: The aim of this Phase IIB single-arm clinical study was to evaluate a protocol using a novel living immune cell drug called “AlloStim^®” in third-line metastatic CRC patients with MSS/pMMR genotype tumors. The protocol was designed to incorporate multiple spatial and temporal immunomodulatory mechanisms, including: enhancing the circulating Th1/Th2 balance; converting immunologically ‘cold’ tumors to ‘hot’ inflamed tumors; creating conditions for immunological cell death and in-situ vaccination aimed at priming a patient-specific, anti-tumor adaptive immune response; and, modifying the tumor microenvironment in order to overcome tumor immunoavoidance and immunosuppression obstacles. Methods: AlloStim^® was administered weekly in intradermal and intravenous doses in 3-five-week cycles, followed by optional monthly intravenous booster infusions. The intradermal AlloStim^® doses are designed to elicit anti-alloantigen-specific Th1 immunity upon rejection of the fully allogeneic AlloStim^® cells by the host. The intravenous doses are designed to cause a rejection response that results in release of systemic inflammatory cytokines that serve to activate by-stander host memory Th1 cells and NK cells. Activated Th1 memory and NK cells extravasate and infiltrate metastatic tumor lesions converting them from ‘cold’ to ‘hot’. The activated NK cells mediate immunological tumor cell death of MHC I negative tumors and the infiltrating Th1 cells create an inflammatory micro-environment, together creating an in-situ anti-tumor vaccine which results in tumor-specific immunity customized to each individual patient. Results: 29 third-line MSS/pMMR metastatic colorectal cancer patients were recruited from 4 cancer centers in the USA. The median overall survival (OS) was 16.4 months (95% CI: 8.6-18mo). Survival at 12 months was 60% and was 39% at 18 months. The immunotherapy was well tolerated with mostly mild treatment-related adverse events. Conclusion: AlloStim^® immunotherapy demonstrated a strong survival signal in immunotherapy-refractory third-line metastatic MSS/pMMR CRC compared to historical controls of active drugs in this indication. These findings support advancement to well-designed, prospective, randomized-controlled clinical studies powered to confirm the survival signal. (ClinicalTrials.gov ID: NCT04444622).

Antiangiogenic drugs may cause vascular normalization and correct hypoxia in tumors, shifting cells to mitochondrial respiration as the primary source of energy. In turn, the addition of an inhibitor of mitochondrial respiration to antiangiogenic therapy holds potential to induce synthetic lethality. This study evaluated the mitochondrial inhibitor ME-344 in combination with bevacizumab in patients with refractory metastatic colorectal cancer (mCRC). Patients were eligible if they had disease progression after standard therapies, adequate hematologic, hepatic and renal function, and no contraindications to bevacizumab. ME-344 was administered intravenously on days 1, 8 and 15 and bevacizumab on days 1 and 15 of 28-day cycles until disease progression or intolerance. The primary efficacy endpoint was progression-free survival (PFS) at week 16. In the 23 patients enrolled, the median age was 58 years, median number of prior lines of therapy was 4, and median interval from last therapy was 3 months. The most common adverse events (all grades/grade ≥ 3) were fatigue (48%/13%), abdominal pain (35%/4%), diarrhea (30%/4%) and constipation (30%/0%). No patient had an objective response; 9 patients (39%) achieved stable disease. The 16-week PFS was 30.6% (95% confidence interval [CI]: 12.2–51.3), the median PFS was 1.9 months (95% CI: 1.6–4.7), and the median overall survival was 6.7 months (95% CI: 3.4-not reached). ME-344 plus bevacizumab was well tolerated. Disease control was limited in this heavily pretreated patient population. Additional investigations in earlier lines are indicated, and extended-release ME-344 formulations may provide longer drug exposure to maximize benefit. (Trial registration number ClinicalTrials.gov NCT05824559. Registration date 22 March 2022).

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by providers and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature, and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and 2 (online only) for more . PURPOSE: To provide evidence-based guidance for clinicians who treat patients with locally advanced rectal cancer. METHODS: A systematic review of the literature published from 2013 to 2023 was conducted to identify relevant systematic reviews, phase II and III randomized controlled trials (RCTs), and observational studies where applicable. RESULTS: Twelve RCTs, two systematic reviews, and one nonrandomized study met the inclusion criteria for this systematic review. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RECOMMENDATIONS: Following assessment with magnetic resonance imaging, for patients with microsatellite stable or proficient mismatch repair locally advanced rectal cancer, total neoadjuvant therapy (TNT; ie chemoradiation [CRT] and chemotherapy) should be offered as initial treatment for patients with tumors located in the lower rectum and/or patients who are at higher risk for local and/or distant metastases. Patients without higher-risk factors may discuss chemotherapy with selective CRT depending on extent of response, TNT, or neoadjuvant long-course CRT or short-course radiation. For patients who are candidates for TNT, the preferred timing for chemotherapy is after radiation, and neoadjuvant long-course CRT is preferred over short-course radiation therapy (RT), however short-course RT may also be a viable treatment option depending on circumstances. Nonoperative management may be discussed as an alternative to total mesorectal excision for patients who have a clinical complete response to neoadjuvant therapy. For patients whose tumors are microsatellite instability-high or mismatch repair deficient, immunotherapy is recommended. Additional information is available at http://www.asco.org/gastrointestinal-cancer-guidelines .

Pathogenic germline variants (PGVs) may be under-detected as causative etiologies in patients with non-small cell lung cancer (NSCLC). The prevalence of PGVs has been reported between 1 and 15% of patients, depending on the patient population. The rate within Hispanic/Latinx populations remains unknown. We retrospectively analyzed the genomic results (Guardant360, Redwood City, CA, USA) of 878 patients with advanced or metastatic NSCLC at five centers in South Florida, USA, from 2019 to 2022 to analyze the rate of incidental PGVs (iPGVs) identified via circulating cell-free tumor DNA (ctDNA). We then stratified the results by tumor histology, age, gender, race, ethnicity, genetic pathway, and co-mutations. Twenty-one iPGVs were identified (21/878 = 2.4%). Among the 21 iPGVs identified, 14 patients were female (66.7%) and 7 were male (33.3%), with a median age of 67 years and tobacco history of 2.5 pack-years. In total, 52.4% of patients identified as Hispanic/Latinx (n = 11) of any race; 19.0% as Ashkenazi Jewish (n = 4), 9.5% as non-Hispanic/Latinx black (n = 2), and 19.0% as non-Hispanic/Latinx white (n = 4). iPGVs in the homologous recombination repair pathway were solely expressed in this cohort (10 ATM, 8 BRCA2, and 3 BRCA1). In total, 76% (16/21) of patients with iPGVs co-expressed somatic alterations, with 56% (9/16) demonstrating alterations in targetable genes. Overall, our real-world findings offer a point prevalence of iPGVs in patients with NSCLC of diverse populations, such as patients who report Hispanic/Latinx ethnicity.

Amyloidosis is a term describing the extracellular deposit of fibrils composed of subunits of several different normal serum proteins in various tissues. Amyloid light chain (AL) amyloidosis contains fibrils that are composed of fragments of monoclonal light chains. Many different disorders and conditions can lead to spontaneous splenic rupture, including AL amyloidosis. We present a case of a 64-year-old woman with spontaneous splenic rupture and hemorrhage. A final diagnosis of systemic amyloidosis secondary to plasma cell myeloma was made with infiltrative cardiomyopathy and possible diastolic congestive heart failure exacerbation. We also provide a narrative review of all documented cases of splenic rupture associated with amyloidosis from the year 2000 until January 2023, along with the main clinical findings and management strategies.