Katie Robinson

In patients with previously treated advanced gastric/gastroesophageal junction adenocarcinoma, chimeric antigen receptor-modified autologous T cells targeting Claudin18.2 (CLDN18.2) (CT041, CARsgen Therapeutics) had a manageable safety/tolerability profile and promising efficacy, according to preliminary data from an ongoing phase 1b/2 study (NCT04581473).

2022 American Society of Clinical Oncology (ASCO) Annual Meeting

, which is taking place from June 3-7 in Chicago, by Changsong QI, MD, PhyD, of Peking University Cancer Hospital & Institute in China.

 is a promising therapeutic target that is often expressed in gastric/gastroesophageal junction cancer. CT041 autologous CAR T-cell injection has shown promising anti-tumor activity in preclinical studies, while results from phase 1 trial suggested that CT041 was well tolerated and had encouraging efficacy in previously treated patients with CLDN18.2-positive advanced gastric/gastroesophageal junction adenocarcinoma. Data from a companion US-based study (NCT04404595) elicited either a response or stable disease in a majority of heavily pretreated patients with CLDN18.2-positive advanced gastric and pancreatic adenocarcinoma, 

results of which were also presented at ASCO 2022

In this open-label, multicenter, phase 1b/2 trial, the researchers assessed the safety, tolerability, and efficacy of CT041 in 14 patients with previously treated CLDN18.2-positive advanced gastric/gastroesophageal junction adenocarcinoma. There are 2 stages in the ongoing study. The phase 1b stage is a dose escalation and dose expansion study and the phase 2 stage is to verify the efficacy and safety of CT041 treatment.

From November 2020 to May 2021, a total of 14 patients (medium age 44.5) with gastric/gastroesophageal junction adenocarcinoma cancer were enrolled in phase 1b. Of the patients, 85.7% had received 2 prior lines of treatment and 14.3% had at least 3 lines. Meanwhile, 57.1% had at least 3 metastatic organs, 92.9% had peritoneal dissemination, and 64.3% had signet ring cell carcinoma. For up to 3 doses of the autologous CAR T-cell injection infusion, 3 of the patients received 3.75 × 10

The most reported adverse events of grade 3 or higher were hematologic toxicity related with lymphodepletion. No dose-limiting toxicities, treatment-related death, neurologic toxicity, or gastrointestinal toxicities were observed. Most occurrences of cytokine release syndrome (CRS) were grade 1 or 2, and 1 patient experienced grade 4 CRS and fully recovered.

Of the patients, 57.1% achieved partial response, 14.3% showed stable disease. With a median follow-up of 8.9 months (95% CI 5.91, NE), the median progression-free survival (PFS) was 5.6 months (95% CI 1.9, 7.4), and median overall survival was 10.8 months (95% CI 5.1, NE). Seven patients were still alive at last follow-up.

This study is ongoing with further investigation of CT041 in phase 2 underway. CARsgen Therapeutics announced in March that the Center for Drug Evaluation of the National Medical Products Administration of China approved the initiation of the CT041 confirmatory phase 2 study.

“The treatment options for gastric cancer patients who have failed at least 2 prior lines are very limited. The median progression-free survival of available therapies, including anti-PD-1 monoclonal antibody, is merely about 2 months, indicating an urgent unmet medical need for more innovative and effective drugs,” said Lin Shen, MD, of Beijing Institute for Cancer Research, the principal investigator. In this early study of CT041 led by our center, themedium “PFS of CT041 was over 5 months, which is very promising data.”

1. QI C, Liu C, Gong J, et al.Safety, tolerability, and preliminary efficacy results in patients with advanced gastric/gastroesophageal junction adenocarcinoma from a phase Ib/II study of CLDN18.2 CAR T-cell therapy (CT041). Presented at: 2022 ASCO Annual Meeting, June 3-7, 2022. Abstract #4017

2. Claudin18.2 CAR T Cells (CT041) Receives Approval to Initiate A Confirmatory Phase II Clinical Trial for advanced GC/GEJ in China. News release. CARsgen Therapeutics, March 3,2022. 

https://www.prnewswire.com/news-releases/claudin18-2-car-t-cells-ct041-receives-approval-to-initiate-a-confirmatory-phase-ii-clinical-trial-for-advanced-gcgej-in-china-301494828.html

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The chimeric antigen receptor-modified autologous T cells targeting CLDN18.2 had a manageable safety/tolerability profile and promising efficacy.

CARsgen Therapeutics’ CT041 Shows Promise in Advanced Gastric/Gastroesophageal Junction Adenocarcinoma 

In patients with multiple myeloma receiving chimeric antigen receptor T cell (CAR-T) therapy, bone marrow minimal residual disease (MRD) negativity was found to be a prognostic factor for survival and response regardless of cellularity and free light chain (FLC) normalization at 1 month.

022 American Society of Clinical Oncology (ASCO) Annual Meeting

, which is taking place from June 3-7, 2022 in Chicago, by Radhika Bansal, MBBS, of the Mayo Clinic in Rochester, Minnesota.

“Hypocellular bone marrow is common in the 3 months post CAR-T,” wrote Bansal and colleagues. “Regardless of bone marrow cellularity, bone marrow MRD negativity at month 1 correlates with deep response and prolonged PFS [progression free survival].” She added that most patients with bone marrow MRD negativity at month 1 also had FLC less than normal. “Bone marrow MRD negativity status and FLC normalization were associated with longer survival,” Bansal wrote.

The authors explained that bone marrow assessment of MRD is prognostic for survival in multiple myeloma, but the timing of this assessment varies across CAR-T therapy trials and differs from standard of care practice. Bone marrow myeloma cell clearance can be detected by month 1 after CAR-T therapy, even before serum immunofixation becomes negative. As bone marrow is still hypocellular at month 1, the prognostic value of MRD negativity at this timepoint is unclear.

In this study, Bansal and colleagues examined the impact of 30-day MRD status in 60 patients (median age 62, male 53%) with multiple myeloma who received CAR-T therapy at the Mayo Clinic between August 2016 and June 2021. Medical records were reviewed retrospectively. The patients underwent a bone marrow biopsy at month 1. Baseline demographics were similar between the bone marrow MRD negative (n=47) and MRD positive (n=13) patients.

Overall, 85% of patients who were bone marrow MRD negative at 1 month had involved/uninvolved FLC less than normal. At 1 month, 40% of all the patients had hypocellular bone marrow. Serial bone marrow samples at months 3, 6 and 12 showed a bone marrow MRD negative rate of 93%, 56% and 58%, and a hypocellularity rate of 54%, 32% and 30%, respectively. Among the bone marrow MRD negative/hypocellular patients at month 1, hypocellular bone marrow was seen in 73% at month 3 and 50% at months 6 and 12.

Patients who were bone marrow MRD negative at month 1 had longer PFS compared with MRD positive patients (17.5 vs. 2.9 months, 

 <.0001). However, PFS was not statistically significantly different between patients who had bone marrow MRD negative and were either hypocellular or not. Bone marrow MRD negative patients with FLC below normal at 1 month had better median PFS compared with those who did not. (MRD-/FLC,<normal 17.9 months, MRD+:2.9 months, MRD-/FLC>normal: 4.9 months; 

“Our data support the continued evaluation of bone marrow early post CAR-T infusion as a prognostic tool,” the authors concluded.

Bansal R, Bakh M, Larsen J, et al. Prognostic value of early bone marrow MRD status in CAR-T therapy for myeloma. Presented at: 2022 ASCO Annual Meeting, June 3-7, 2022. Abstract #8022

Regardless of bone marrow cellularity, bone marrow minimal residual disease (MRD) negativity at month 1 correlated with deep response and prolonged PFS.

Early Bone Marrow MRD Status May Determine CAR-T Therapy Response in Myeloma

In patients with progressive multiple myeloma after 1 to 3 prior lines of therapy, a single ciltacabtagene autoleucel (cilta-cel)infusion led to deepening and durable responses at 17.1 months follow-up in this difficult-to-treat population with a poor prognosis. This is according to the updated clinical data from Cohort A of the ongoing multicohort phase 2 CARTITUDE-2 study (NCT04133636).

, which is taking place from June 3-7, 2022 in Chicago, by Hermann Einsele, MD, of Universitätsklinikum Würzburg in Germany.

In February, cilta-cel (CARVYKTI, Jansen Biotech, Legend Biotech), a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapy, received FDA approval for the treatment of adults with relapsed or refractory multiple myeloma after 4 or more prior lines of therapy.

CARTITUDE-2 is evaluating the safety and efficacy of cilta-cel in various multiple myeloma settings including earlier lines. Cohort A of the study is evaluating cilta-cel safety and efficacy in patients with multiple myeloma who received 1 to 3 prior lines of therapy, including a proteasome inhibitor and immunomodulatory agent, and who are lenalidomide-refractory and have had no prior exposure to BCMA-targeting agents.

As of January 2022 (median follow-up 17.1 months), 20 patients (65% male, median age 60) received a single cilta-cel infusion (target dose 0.75×106 CAR+ viable T cells/kg)

post lymphodepletion. Safety and efficacy were assessed, and the primary end point was minimal residual disease (MRD) negativity at 10-5.

The overall response rate (ORR) was 95%, while 90% achieved a complete response

(CR) or better, and 95% had a very good partial response (VGPR) or better. The median times to first and best response were 1 month and 2.6 months, respectively. Of the patients, 16 were MRD-evaluable, all of whom achieved MRD negativity at 10-5. The median duration of response (DOR) was not reached and the 12-month event-free rate was 79%. The 12-month progression free survival (PFS) rate was 75%.

Meanwhile, the median time to onset of cytokine release syndrome was 7 days and it occurred in 95% of patients, with median duration of 3 days. The rates of neurotoxicity and immune effector cell-associated neurotoxicity syndrome (ICANS) were 30% and 15%, respectively, while 1 patient had grade 2 facial paralysis.

One death occurred due to COVID-19, while 2 were due to progressive disease, and 1 was due to sepsis that was unrelated to the treatment.

The updated data from the CARTITUDE-2 study “demonstrates the promise of cilta-cel in earlier lines of treatment,” said Ying Huang, PhD, chief executive officer of Legend Biotech.

This patient population is being further evaluated in the CARTITUDE-4 study (NCT04181827).

1. Einsele H, Cohen A, Delforge M, et al.Biological correlative analyses and updated clinical data of ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR-T cell therapy, in lenalidomide (len)-refractory patients (pts) with progressive multiple myeloma (MM) after 1–3 prior lines of therapy (LOT): CARTITUDE-2, cohort A. Presented at: 2022 ASCO Annual Meeting, June 3-7, 2022. Abstract #8020

2. U.S. FDA Approves CARVYKTI™ (ciltacabtagene autoleucel), Janssen’s First Cell Therapy, a BCMA-Directed CAR-T Immunotherapy for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma. News release. Janssen Biotech. February 28,2022.

https://www.jnj.com/u-s-fda-approves-carvykti-ciltacabtagene-autoleucel-janssens-first-cell-therapy-a-bcma-directed-car-t-immunotherapy-for-the-treatment-of-patients-with-relapsed-or-refractory-multiple-myeloma

3. Legend Biotech to Highlight Continued Progress in the Treatment of Multiple Myeloma With Updated Data From BCMA CAR-T Studies at 2022 ASCO and EHA. News release. Legend Biotech. May 18, 2022.

https://www.businesswire.com/news/home/20220518005307/en/

Cohort A of the CARTITUDE-2 study is evaluating cilta-cel safety and efficacy in patients with multiple myeloma who received 1 to 3 prior lines of therapy.

Cilta-Cel Shows Promise in Earlier Lines of Treatment in Patients With Progressive Multiple Myeloma 

In patients with large B-cell lymphoma (LBCL), treatment with axicabtagene ciloleucel (axi-cel;Yescarta; Kite Pharma, Gilead) was associated with a favorable overall survival (OS), progression free survival (PFS), and safety profile regardless of race or ethnicity, according to data from a real-world setting presented at the 

, taking place June 3-7, 2022 in Chicago.

“No notable differences in outcomes were observed for Hispanic or Asian patients,” wrote Frederick L. Locke, MD, of the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida, and colleagues. “Lower response rates in African American patients noted here warrant further investigation including any underrepresentation not explained by a lower incidence rate for diffuse LBCL, access to care, and disease burden.”

In April, the FDA approved axi-cel for the treatment of adult patients with LBCL that is refractory to first-line chemoimmunotherapy or who experienced relapse within 12 months of first-line chemoimmunotherapy.

Locke and colleagues explained that there is a lack of data on outcomes by race and ethnicity from studies of CAR T-cell therapies. They examined outcomes by race (African American or Asian vs White) and ethnicity (Hispanic vs. non-Hispanic) among 1389 patients with LBCL who received axi-cel in a real-world setting between October 2017 and August 2020.

Of the patients, 1127 (81%) were White, 81 (6%) were Asian, and 70 (5%) were African American; 152 (11%) were Hispanic including 104 White, 2 Black, and 1 Asian Hispanic. Patients with a history of prior nonhematopoietic cell transplantations cellular therapy, primary central nervous system lymphoma, and unknown comorbidity were excluded from the trial. African American patients compared with White patients were younger (median age 55.5 vs. 62.8 years), more likely to have pulmonary impairment, (41% vs. 28%) and tended to have longer time from diagnosis (≥ 12 months 71% vs. 59%). Hispanic patients were younger (median age 58.5 vs. 62.6 years) than non-Hispanic patients.

The median follow-up was 12.7 months. Outcomes included overall response rate (ORR), complete response (CR) rate, duration of response (DOR), PFS and OS, grade ≥ 3 cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). ORR and CR were evaluated in patients with at least 180 days of follow-up.

The ORR was 74% (CR 57%, 12-month PFS and OS 48% and 63%) for White, 57% (CR 45%, 12-month PFS and OS 36% and 62%) for African American, 67% (CR 53%, 12-month PFS and OS 55% and 65%) for Asian and 73% (CR 55%, 12-month PFS and OS 50% and 65%) for Hispanic patients. Grade ≥ 3 CRS and ICANS occurred in 7% and 18% of African American, 10% and 19% of Asian, and 8% and 27% of White patients, respectively. Hispanic patients had lower rates of grade ≥ 3 CRS and ICANS (4% and 15%) compared with non-Hispanic patients (9% and 27%).

African American race was associated with inferior ORR (OR 0.40; 95% CI, 0.24-0.69) and CR rate (OR 0.55; 95% CI 0.32-0.93) compared with White. Asian patients had favorable DOR compared with both White race (HR 0.46; 95% CI 0.24-0.87) and African American patients (HR 0.39; 95% CI 0.17-0.88). 

No statistical differences were found in OS and PFS across races, nor in any efficacy outcome between Hispanic and non-Hispanic patients. Asian (OR 0.52; 95% CI 0.29-0.96 vs. White) and Hispanic patients (OR 0.51; 95% CI 0.31-0.85 vs. non-Hispanic) had lower risk of grade ≥ 3 ICANS.

For more coverage of ASCO 2022, click here. 

1. Locke F, Siddiqi T, Jacobson C, et al. Real-world outcomes of axicabtagene ciloleucel (Axi-cel) for the treatment of large B-cell lymphoma (LBCL) by race and ethnicity. Presented at: 2022 ASCO Annual Meeting, June 3-7, 2022. Abstract #7571

2. FDA approves axicabtagene ciloleucel for second-line treatment of large B-cell lymphoma. News Release. April 1, 2022. U.S. Food & Drug Administration. 

https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-axicabtagene-ciloleucel-second-line-treatment-large-b-cell-lymphoma

No differences were found in overall survival and progression free survival across races.

Axi-Cel Shows Favorable Outcomes in Large B-Cell Lymphoma Regardless of Race, Ethnicity

Hematopoietic reconstitution after myeloablative conditioning and transplantation may be entirely driven by hematopoietic stem cells (HSCs), according to a preclinical study presented at the 

2022 American Society of Gene and Cell Therapy Annual Meeting

, taking place May 16-19, 2022, in Washington, DC.

“These findings have major implications for HSC transplantation and particularly for HSC gene therapy,” reported Stefan Radtke, PhD, of Fred Hutchinson Cancer Research Center in Seattle, and colleagues. “The ability to directly modify a highly enriched CD34+CD90+ cell population to accomplish both short and long-term engraftment would substantially reduce the typically large and expensive amount of vectors or editing agents needed for the genetic engineering of HSCs.”

Recovery after HSC transplantation has been believed for decades to be biphasic, with short-term progenitors driving recovery for the first 6-9 months and multipotent HSCs providing long-term repopulation. Data from human gene therapy trials have used retroviral integration site analysis to track gene-marked cells seeming to confirm this biphasic model.

The investigators performed high-density sampling for retroviral integration site analysis in 2 nonhuman primates, who were followed for 4.5 years. HSC clone signatures were collected and HSC contribution was identified in very early samples to determine the onset of HSC contribution and investigate the kinetics of hematopoietic recovery. The contribution of multipotent HSCs clones was detected during neutrophil recovery ­— a finding is in contrast with the current biphasic model. Moreover, multipotent HSCs became the dominant source for mature blood cells in the peripheral blood as early as 50 days post-transplant.

Further, a hematopoietic reconstitution simulation, informed by observed changes in clonal diversity 

, also predicted that hematopoietic recovery is primarily HSC driven and that HSC contribution follows a random pattern. Lastly, 

 experiments in colony-forming cell assays confirmed that HSCs proliferation and differentiation is a random process.

The investigators noted that the observed changes in the clonal diversity during early recovery suggest a random HSC engraftment and differentiation pattern. Early blood production is driven by HSC clones that are not predetermined but randomly contribute to a limited number of lineages before they disappear—a cell population incorrectly identified as lineage-restricted short-term progenitors, they concluded.

1. Radtke S, Enstrom M, Pande D, et al. Short- and Long-Term Hematopoietic Reconstitution After Transplantation is Stem Cell-driven and Stochastic: Implications for Gene Therapy. Presented at: American Society of Gene & Cell Therapy 25th Annual Meeting; May 16-19, 2022; Washington, DC. Accessed May 17, 2022. 

https://annualmeeting.asgct.org/abstracts/abstract-details?abstractId=6705

2. Six E, Guilloux A, Denis A, et al. Clonal tracking in gene therapy patients reveals a diversity of human hematopoietic differentiation programs. 

Findings from a preclinical study, which are in contrast with the current biphasic recovery model, have implications for both HSC transplantation and gene therapy.

Hematopoietic Recovery After Myeloablative Transplantation May Be Entirely Driven by Hematopoietic Stem Cells

In a phase 1, first-in-human study, investigators are evaluating the safety, tolerability and preliminary efficacy of an anti-human epidermal growth factor receptor 2 (HER2) chimeric antigen receptor (CAR) macrophage therapy, CT-0508 (Carisma Therapeutics), in participants with solid tumors and HER2 overexpression.

A brief outline of the trial and the investigational therapy were presented by Yara Abdou, MD, of the University of North Carolina Lineberger Comprehensive Cancer Center, at the 

, taking place May 16-19, 2022 in Washington, DC.

“Adoptive T cell therapies have led to remarkable advances among patients with hematologic malignancies, but with less success in those with solid tumors,” the investigators reported.

Since macrophages are abundant in the solid tumor microenvironment, it has been hypothesized that they can be engineered to be proinflammatory, serving as an ideal vector for adoptive solid tumor cellular therapy. Insertion of a CAR on the macrophages allows them to recognize and ingest antigen-overexpressing cancer cells, reprogram the solid tumor microenvironment, and present neoantigens to T cells, resulting in epitope spreading and improved immune memory. Meanwhile, HER2 overexpression is known to promote tumorigenesis in many solid tumors, notably in bladder, gastric, breast and ovarian tumors.

CT-0508 comprises autologous monocyte-derived proinflammatory macrophages expressing an anti-HER2 CAR. In pre-clinical studies, CT-0508 induced targeted cancer cell phagocytosis while sparing normal cells, decreased tumor burden, prolonged survival, and was safe and effective in a semi-immunocompetent mouse model of human HER2 overexpressing ovarian cancer. In September 2021, the FDA granted a fast-track designation to CT-0508 for use as a potential therapeutic option for patients with solid tumors.

The study, which is also evaluating the cell manufacturing feasibility and trafficking, will include 18 participants with locally advanced or metastatic solid tumors overexpressing HER2, with progression on available therapies. Group 1 participants will receive CT-0508 infusion split over day 1, 3 and 5, while those in group 2 will receive the full CT-0508 infusion on day 1. The researchers will collect pre and post treatment biopsies and blood samples to investigate correlates of safety, trafficking, CT-0508 persistence in blood and in the tumor, target antigen engagement and tumor microenvironment modulation immune response.

In November 2021, Carisma Therapeutics presented preliminary findings from the trial, demonstrating that CT-0508 was well tolerated after infusion, with no dose limiting toxicities. “We will continue to enroll patients in the landmark clinical trial of CT-0508,” said Debora Barton, MD, chief medical officer at Carisma Therapeutics, at that time.

1. Abdou Y, Yuan Y, Ueno N, et al. A Phase 1, First in Human (FIH) Study of Adenovirally Transduced Autologous Macrophages Engineered to Contain an Anti-HER2 Chimeric Antigen Receptor (CAR) in Subjects with HER2 Overexpressing Solid Tumors. Presented at: American Society of Gene & Cell Therapy 25th Annual Meeting; May 16-19, 2022; Washington, DC. Accessed May 17, 2022. https://annualmeeting.asgct.org/abstracts/abstract-details?abstractId=6702

2. CARISMA Therapeutics announces US Food and Drug Administration grants fast track designation to CT-0508 for the treatment of patients with solid tumors. News release. CARISMA Therapeutics, Inc. September 22, 2021. Accessed May 17, 2022. 

https://carismatx.com/carisma-therapeutics-announces-u-s-food-and-drug-administration-grants-fast-track-designation-to-ct-0508-for-the-treatment-of-patients-with-solid-tumors/

3. Carisma Therapeutics Presents Data from Phase I Clinical Trial of CT-0508, A HER2 Targeted CAR-Macrophage. News Release. CARISMA Therapeutics, Inc. November 12, 2021. Accessed May 17, 2022. 

https://carismatx.com/carisma-therapeutics-presents-data-from-phase-i-clinical-trial-of-ct-0508-a-her2-targeted-car-macrophage/

Investigators are evaluating the safety, tolerability and preliminary efficacy of CT-0508 in patients with solid tumors and HER2 overexpression.

CAR Macrophage Therapy for HER2 Solid Tumors Continues Through First in Human Trial

In patients with refractory B-cell lymphoma, thoracic imaging findings correlated with cytokine release syndrome grade following chimeric antigen receptor (CAR) T-cell infusion. This is according to a study published in 

 which also showed that CAR T-cell therapy yielded high rates of imaging-based treatment response.

“Imaging plays a critical role in the evaluation of clinical cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome (ICANS) toxicity following CAR T-cell treatment,” wrote Daniel Smith, M.D., a radiologist at the University Hospitals Cleveland Medical Center in Ohio. “Specific findings at thoracic imaging—in particular, pleural effusion and atelectasis—may prove useful correlates for severe clinical grades of cytokine release syndrome, while findings related to ICANS tend to be less specific and less frequent. “

CAR T-cell immunotherapy is increasingly used for refractory lymphoma, but it may lead to cytokine release syndrome and ICANS in the early period following infusion. The associations between cytokine release syndrome or ICANS grade and imaging findings are not established. The goal of this study was to characterize thoracic and neuroimaging findings associated with cytokine release syndrome and ICANS in patients with refractory B-cell lymphoma.

The retrospective analysis included 38 patients (mean age 59; 61% men) with refractory B-cell lymphoma who underwent CAR T-cell infusion. Of these, 63% and 29% experienced clinical grade 1 or higher cytokine release syndrome and ICANS, respectively. Patients with grade 2 or higher cytokine release syndrome were more likely to have thoracic imaging evidence — at radiography, CT and/or MRI — of pleural effusions (36% vs 8.3%, P = .04) and atelectasis (57% vs 25%, P = .048) than patients without cytokine release syndrome or with grade 1 toxicity. Positive imaging findings were identified in 43% with grade 2 or higher ICANS who underwent neuroimaging. Patients undergoing CAR T-cell therapy had higher rates of clinical response, including 56% with complete response and 19%with partial response.

“Our findings further highlight the central role of PET/CT in disease response after CAR-T cell therapy,” the authors wrote.

Limitations of the study included its retrospective design, small sample size, and that most patients without toxicity did not undergo imaging.

 Mark Langer, M.D., professor of clinical radiation oncology at Indiana University School of Medicine, wrote that “in the study by Smith et al, atelectasis and pleural effusions were more common in patients with severe cytokine release syndrome than in those with mild or absent cases. Edema and airway consolidation were not more common.” He added, “Whether such features emerge only when the case becomes clinically more severe or whether these features are early signs of disease that will eventually evolve into a higher-grade condition is a question deserving of future study.

“As more data are prospectively obtained, imaging guidelines to better monitor for the important conditions examined here may be established, and the information collected used to effectively intervene early in detection and treatment,” Dr. Langer wrote.

PET/CT plays a central role in evaluating response after CAR T-cell therapy. 