Pathological landscape of tumor flare reaction to epcoritamab treatment.

Tumor flare reaction (TFR) is characterized by an increase in lesion size during immune-based therapy, often resembling disease progression. It signifies inflammation at the tumor site and is frequently seen in immunotherapy, where it is termed "tumor pseudoprogression." The exact mechanisms behind TFR remain unclear. We report the case of a 62-year-old Japanese man with relapsed and refractory diffuse large B cell lymphoma treated with epcoritamab. On day 10 of the first epcoritamab cycle, after two subcutaneous injections of epcoritamab, the cutaneous lymphoma lesions became swollen. This was identified as TFR, and was managed with a three-day course of intravenous dexamethasone at 12 mg/day. The third injection, scheduled for day 15, was delayed by 1 week. Four doses of epcoritamab were completed over the initial 35-day period. A skin biopsy was performed on day 30. Histopathological examination showed CD20+ large atypical lymphocytes forming residual nodules, encircled by CD4+ and CD8+ lymphocytes, with a predominance of CD8+ T cells over CD4+ T cells. Although infrequent, TFR may be a significant indicator of tumor response to epcoritamab therapy. The diagnosis of TFR could be underestimated, and proper identification and understanding of its clinicopathological features are crucial for its effective management.

Reactions and adverse events induced by T-cell engagers as anti-cancer immunotherapies, a comprehensive review.

T-cell engagers (TCE) are cancer immunotherapies that have recently demonstrated meaningful benefit for patients with hematological malignancies and solid tumors. The anticipated widespread use of T cell engagers poses implementation challenges and highlights the need for guidance to anticipate, mitigate, and manage adverse events. By mobilizing T-cells directly at the contact of tumor cells, TCE mount an obligatory and immediate anti-tumor immune response that could result in diverse reactions and adverse events. Cytokine release syndrome (CRS) is the most common reaction and is largely confined to the first drug administrations during step-up dosage. Cytokine release syndrome should be distinguished from infusion related reaction by clinical symptoms, timing to occurrence, pathophysiological aspects, and clinical management. Other common reactions and adverse events with TCE are immune effector Cell-Associated Neurotoxicity Syndrome (ICANS), infections, tumor flare reaction and cytopenias. The toxicity profiles of TCE and CAR-T cells have commonalities and distinctions that we sum-up in this review. As compared with CAR-T cells, TCE are responsible for less frequently severe CRS or ICANS. This review recapitulates terminology, pathophysiology, severity grading system and management of reactions and adverse events related to TCE.

Comparing the Intensity of Pain and Incidence of Flare Reaction Following Trigger Finger Injections Using Betamethasone and Methylprednisolone: A Double-Blinded, Randomized Controlled Trial.

BACKGROUND: Considerable evidence supports corticosteroid injection as an effective treatment for trigger finger. One common side effect, the flare reaction, is a well-documented phenomenon of increased pain following steroid injections. Its incidence and intensity may be related to steroid composition. The purpose of this study was to determine whether betamethasone and methylprednisolone injections for trigger fingers have differing intensity of pain or incidence flare reaction. METHODS: Patients with symptomatic trigger finger were recruited during their hand surgery visits. Patients were randomized into 2 treatment groups: betamethasone (40 mg) and methylprednisolone (6 mg) mixed with lidocaine 1%. Treatment group assignment was blinded to the patients and investigators. Visual analog scale pain measurements were taken prior to injection, 5 minutes postinjection, and daily thereafter for 7 days. RESULTS: Sixty-four patients were randomized into the 2 treatment groups. Patients in the betamethasone group reported slightly higher baseline pain compared with the methylprednisolone group, but lower pain on day 1. None of the following days showed a statistically significant difference. CONCLUSIONS: The incidence of flare and severe flare reactions of betamethasone injections for trigger finger management was roughly double that of methylprednisolone, but this difference was not statistically significant. Further studies are required to evaluate the relative course of nonflare postinjection pain for different corticosteroid injections for trigger finger injections.

Comparison of triamcinolone and methylprednisolone efficacy and steroid flare reaction rates after shoulder corticosteroid injection: a prospective interrupted time series study.

BACKGROUND: A corticosteroid flare reaction is a well-described phenomenon that causes significant pain and dysfunction. The paucity of literature impedes decision making regarding which corticosteroid to use for shoulder injection. The purpose of this study was to compare methylprednisolone acetate (MPA) and triamcinolone acetonide (TA) injections in the glenohumeral joint and/or subacromial space in terms of efficacy and the incidence of steroid flare reactions. METHODS: In this prospective, interrupted time series, parallel study, patients received injections in the glenohumeral joint and/or subacromial space. MPA and TA were used during 2 discrete 3-month periods. The injections consisted of 2 mL of lidocaine, 2 mL of bupivacaine, and 80 mg of either MPA or TA. Visual analog scale (VAS) pain scores were recorded immediately before injection; 1-7 days after injection; and 3, 6, and 12 months after injection. The primary outcome was the incidence of a steroid flare reaction, defined as a post-injection increase in the VAS score by ≥2 points. The secondary outcome was injection failure, defined as a post-injection VAS score greater than the baseline score or the need for another intervention. We used linear mixed models with a patient-level random intercept to identify the mean VAS score change for TA injections in the first week after injection. RESULTS: MPA or TA shoulder injections were administered in 421 patients; of these patients, 15 received bilateral-joint injections whereas 406 received a single-joint injection, for a total of 436 injections (209 MPA and 227 TA injections). Pain scores in the first week after injection were available for 193 MPA and 199 TA injections. Significantly more patients in the MPA cohort reported flare reactions compared with the TA cohort (22.8% vs. 4.0%, P < .001) during the first week after injection. In the first week after injection, the mean VAS score of patients receiving TA injections was 1.05 (95% confidence interval, 0.47-1.63) lower than that of patients receiving MPA injections when adjusted for age, sex, race, pain type, surgeon type, and injection site. At 3 months, surveys for 169 MPA and 172 TA injections were completed, with no significant difference in the rate of injection failure for MPA vs. TA (42.6% vs. 36.1%, P = .224). Treatment failure rates were significantly higher for MPA than for TA at 6 months (78.44% vs. 62.5%, P < .001) but not at 12 months (81.18% vs. 81.42%, P = .531.) CONCLUSION: TA injections resulted in a >5-fold reduction in steroid flare reactions, with statistically superior 6-month efficacy rates, compared with MPA injections. This study supports TA as a more viable corticosteroid option for shoulder injection.

Transient atelectasis due to hilar lymph node swelling affected by lenalidomide-induced tumor flare reaction.

Tumor flare reaction (TFR) is a unique immune-mediated tumor recognition phenomenon presenting as rapid enlargement of the tumor, which mimics disease progression, developing in the early stage of treatment using immunomodulatory drugs or immune checkpoint inhibitors. A 59-year-old man with follicular lymphoma had residual tumor burden in the left hilar lymph nodes after R-CHOP therapy, and received lenalidomide and rituximab (R2) therapy. He developed respiratory distress on day 11 of R2 therapy. Chest X-ray and CT demonstrated left lung atelectasis due to left hilar lymph node swelling. We performed transbronchial lung biopsy on day 20 of R2 therapy. The biopsied left bronchus tissue exhibited extensive necrosis, which had a B-cell phenotype consistent with that of follicular lymphoma. Neither NK cells nor cytotoxic T cells were detected. It was unclear whether the immune effector cells disappeared at the time of transbronchial lung biopsy. Atelectasis in our patient improved by continuing R2 therapy beyond TFR.

Tumor Flare Reaction in a Classic Hodgkin Lymphoma Patient Treated With Brentuximab Vedotin and Tislelizumab: A Case Report.

Background: Tumor flare reaction (TFR) is a clinical syndrome, which is mainly associated with painful and swollen lymph nodes or splenomegaly, slight fever, bone pain, and skin rash during treatment with immune-related drugs, causing difficulty in distinguishing TFR from disease progression. Brentuximab vedotin (BV) and programmed death 1 (PD-1) inhibitor are two ideal drugs used for the treatment of classic Hodgkin lymphoma, but few studies have reported their adverse effects in association with TFR. The efficacy and safety of monotherapy or combination therapy with these drugs needs to be further evaluated. It is essential to determine whether treated patients can develop TFR, thus enabling more accurate diagnosis and treatment. Case presentation: A 26-year-old female patient, diagnosed with classic Hodgkin lymphoma, had received 2 + 3 cycles of ABVD chemotherapy (a combination of adriamycin, bleomycin, vinblastine, and dacarbazine) and 4 cycles of PD-1 inhibitor (tislelizumab) therapy but exhibited poor efficacy. Subsequently, she was given combination therapy of BV (100 mg) + tislelizumab (200 mg). However, a slight fever, painful and swollen axillary lymph nodes, multiple skin rashes with pruritus, joint pain, and fatigue with poor appetite appeared during the treatment. Ultrasound (US) scans revealed that multiple lymph nodes were significantly enlarged. After treatment with low-dose dexamethasone and cetirizine, the symptoms were alleviated. A biopsy of the left axillary lymph node revealed that lymphoid tissue exhibited proliferative changes, without tumor cell infiltration. These findings were consistent with the clinical and pathological manifestations of TFR. Conclusion: Combination therapy with BV and PD-1 inhibitor was effective in the treatment of relapsed or refractory classic Hodgkin lymphoma. The results suggest that the combination therapy may cause TFR, and biopsy and also continuous imaging observation are important to determine the disease stage. This approach allows clinicians to decide whether to continue the current treatment plan, and alerts them to the occurrence of excessive activation of the immune system.

Venous Flare Reactions: A Case Report of Reactions Following Etoposide Infusion.

Venous flare reaction, a localized allergic response associated with the administration of an irritant, is one of the most common chemotherapy infusion-related reactions. Etoposide, a drug commonly used in patients with lung cancer, has been reported to be an irritant with vesicant properties depending on the volume administered. This article presents the case of a patient who has a venous flare reaction immediately following the administration of etoposide for the treatment of diffuse large B-cell lymphoma. Managing such complications is crucial to maintaining patient safety. Proper training and education should be incorporated into nursing practice when identifying, preventing, and managing such reactions.

Effect of ice on pain after corticosteroid injection in the hand and wrist: a randomized controlled trial.

This prospective, randomized controlled study was designed to determine if applying ice to the site of corticosteroid injections in the hand and wrist reduces post-injection pain. Patients receiving corticosteroid injections in the hand or wrist at a tertiary institution were enrolled. Subjects were randomized to apply ice to the injection site and take scheduled over-the-counter analgesics ( n = 36) or take scheduled over-the-counter analgesics alone ( n = 32). There were no significant differences in the mean pain score between the two groups at any time-point (pre-injection or 1-5 days post-injection). In regression modelling, the application of ice did not predict pain after injection. Visual analogue pain scores increased at least 2 points (0-10 scale) after injection in 17 out of 36 patients in the ice group versus ten out of 32 control patients. We conclude that the application of ice in addition to over-the-counter analgesics does not reduce post-injection pain after corticosteroid injection in the hand or wrist. LEVEL OF EVIDENCE: I Therapeutic Study.

The incidence of postoperative flare reaction and tissue complications in Dupuytren's disease using tension-free immobilization.

PURPOSE: Open fasciectomy represents a standard treatment of Dupuytren's disease. Although patients are commonly immobilized in extension to prevent postoperative contracture formation, immobilizing the extremity under tension may precipitate a flare reaction and scar-related complications. This study explores the incidence of flare reaction and other complications with postoperative tension-free splinting after fasciectomy for Dupuytren's contracture. METHODS: We retrospectively reviewed patients' charts that consisted of 228 procedures in 191 patients who underwent surgery by the senior author between 2000 and 2010. Postoperative notes were reviewed for wound healing problems, scar appearance, flare reaction, and complications. The grading system defined by Evans et al. was used to standardize flare reaction and scar complications. RESULTS: Using tension-free splinting, the incidence of flare reaction was 3.5 % (8/228). The eight patients that had flare reactions had mild involvement, and no severe reaction was observed. Fifteen patients had hypertrophic scars, eight had hypersensitive scars, and six had recurrent contractures. CONCLUSIONS: The incidence of flare reaction using tension-free immobilization postoperatively was low in our study. According to our findings, wound healing problems are rare when tensionless splinting is utilized. Type of study/level of evidence Case series, Level IV, Therapeutic study.