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

2022 ◽  
Vol 12 ◽  
Chunting Zhu ◽  
Yi Zhao ◽  
Fang Yu ◽  
Weijia Huang ◽  
Wenjun Wu ◽  

BackgroundTumor 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 presentationA 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.ConclusionCombination 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.

ISRN Oncology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Rungnapa Chairat ◽  
Adisorn Puttisri ◽  
Asani Pamarapa ◽  
Jirause Moollaor ◽  
Chamaiporn Tawichasri ◽  

Objective. To explore prognostic characteristics for locoregional recurrence, distant recurrence, and mortality in patients with breast cancer. Methods. A 5-year retrospective review of patients was conducted in two university affiliated hospitals in the north of Thailand. Prognostic characteristics and clinical outcomes were retrieved from medical registry. Death was verified by the civil database from the Ministry of Interior, direct telephone contact, or by prepaid postcard. Data were analyzed by stratified Cox’s regression proposed by Lunn & McNeil, in which multiple-typed outcomes were analyzed in a single multivariable model. Results. The assembled cohort comprised 829 patients. Under the multivariable analysis, 7 prognostic characteristics were significant prognostic indicators. Positive axillary lymph nodes >3 and presence of lymphovascular invasion (LVI) increased locoregional recurrence, while disease stage 3, positive axillary lymph nodes >3, and radiotherapy increase distant recurrence. Hormonal therapy reduced the distant recurrence. Pathological tumor size >2 cm, disease stage 3, positive axillary lymph nodes >3, and presence of LVI increased, while hormonal therapy and chemotherapy reduced death. Conclusions. Clinical characteristic reflecting tumor invasions increased locoregional recurrence, distant recurrence, or death, while hormonal therapy and chemotherapy reduced such risks. The effect of radiation remained inconclusive but may increase the risk of distant recurrence.

1999 ◽  
Vol 17 (10) ◽  
pp. 3033-3037 ◽  
Kathy D. Miller ◽  
Worta McCaskill-Stevens ◽  
Judy Sisk ◽  
David M. Loesch ◽  
Frank Monaco ◽  

PURPOSE: To evaluate the efficacy and toxicity of combination and sequential dose-dense chemotherapy with doxorubicin and docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) as primary chemotherapy of breast cancer. PATIENTS AND METHODS: Patients with newly diagnosed stage II or noninflammatory stage III breast cancer were randomly assigned to receive the same total doses of doxorubicin and docetaxel over a 12-week period before definitive surgery. Patients in arm A received sequential therapy with doxorubicin 75 mg/m2 every 2 weeks for three cycles followed by docetaxel 100 mg/m2 every 2 weeks for three cycles. Patients in arm B received combination therapy with doxorubicin 56 mg/m2 plus docetaxel 75 mg/m2 every 3 weeks for four cycles. Granulocyte colony-stimulating factor was administered on days 2 to 12 of each cycle in both groups. RESULTS: Forty patients were entered onto the trial. Pretreatment tumor size averaged 5.7 cm with clinicallypositive axillary lymph nodes in 23 patients (57%). As expected, myelosuppression was severe in both groups; however, ≥ 80% of planned dose-intensity was delivered. Hand-foot syndrome was more common after sequential therapy. Clinical responses were similar in both groups, with an overall response rate of 87%, including 20% clinical complete remissions. Pathologic complete remission or residual in situ disease only was confirmed in five patients (12.8%). Patients who received sequential therapy had fewer positive lymph nodes (mean, 2.17 v 4.81; P < .037) at definitive surgery. CONCLUSION: Primary chemotherapy with doxorubicin and docetaxel is well tolerated and highly active. A sequential treatment schedule increases toxicity but may result in more substantial lymph node clearance than combination therapy.

2019 ◽  
Vol 37 (17) ◽  
pp. 1479-1489 ◽  
Jing Nie ◽  
Chunmeng Wang ◽  
Yang Liu ◽  
Qingming Yang ◽  
Qian Mei ◽  

PURPOSE Anti–programmed death-1 (PD-1) monotherapy induces a high response rate in patients with relapsed/refractory classic Hodgkin lymphoma (cHL), but complete remission (CR) is infrequently observed. As decitabine is known to boost T-cell function, we assessed the safety and efficacy of anti–PD-1 camrelizumab alone versus decitabine-primed camrelizumab in patients with relapsed/refractory cHL. METHODS This two-arm, open-label, phase II study enrolled patients with relapsed/refractory cHL who had received at least two lines of previous therapy. Anti–PD-1 treatment-naïve patients were randomly assigned (1:2) to camrelizumab (200 mg) monotherapy or decitabine (10 mg/d, days 1 to 5) plus camrelizumab (200 mg, day 8) combination therapy every 3 weeks. Patients who were previously treated with anti–PD-1 were assigned combination therapy. Primary end point was CR rate and safety. RESULTS Overall, 86 patients were enrolled and evaluated for response, with a median follow-up of 14.9 months. In anti–PD-1–naïve patients, CR rate was 32% (six of 19 patients) with camrelizumab monotherapy versus 71% (30 of 42 patients) who were administered decitabine plus camrelizumab ( P = .003). At the time of analysis, the response duration rate at 6 months was 76% on camrelizumab monotherapy versus 100% on decitabine plus camrelizumab. For patients who were previously treated with anti–PD-1, 28% achieved CR and 24% partial response after decitabine plus camrelizumab. Ten patients maintained a response at more than 6 months and 81% of responders were estimated to have a response at more than 1 year. For both treatments, the most common adverse events were clinically inconsequential cherry hemangiomas and leukocytopenia that were self-limiting. CONCLUSION CR rate in patients with relapsed/refractory cHL who were clinically naïve to PD-1 blockade was significantly higher with decitabine plus camrelizumab than with camrelizumab alone. Decitabine plus camrelizumab may reverse resistance to PD-1 inhibitors in patients with relapsed/refractory cHL.

2017 ◽  
Vol 35 (22) ◽  
pp. 2467-2470 ◽  
Matthew M. Poppe ◽  
Jayant P. Agarwal

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 45-year-old premenopausal woman presented with multifocal cancer in the right breast, with lesions at 1:00 and 4:00, the largest measuring approximately 3 cm on exam, and multiple palpable right axillary lymph nodes. A core biopsy confirmed invasive ductal carcinoma, grade 2 of 3, that was estrogen receptor positive, progesterone receptor positive, and HER2 negative. Fine needle aspiration of a right axillary node confirmed metastatic carcinoma. A positron emission tomography (PET)/ computed tomography done before starting chemotherapy demonstrated an absence of metastatic disease with expected avidity in two separate breast masses and multiple conglomerated 1-2 cm level I and II axillary lymph nodes. She received neoadjuvant chemotherapy with doxorubicin plus cyclophosphamide, followed by paclitaxel, and had a complete clinical response with resolution of the breast and axillary masses on exam. A repeat PET/computed tomography demonstrated reduced size of the breast and axillary disease, and no significant residual PET avidity. Her breast surgeon recommended a right mastectomy with axillary node dissection. As part of her multidisciplinary treatment plan, she consulted with two plastic surgeons to discuss reconstruction options. Plastic Surgeon A advised placement of an implant at the time of mastectomy while Surgeon B contrasted the pros and cons of an autologous transverse rectus abdominis muscle flap reconstruction with an implant based reconstruction. Surgeon B believed that autologous reconstruction would yield the best long-term cosmetic outcome. Before making her surgery decision, the patient consulted with a radiation oncologist to discuss the effect radiation may have on her reconstruction outcome.

2017 ◽  
Vol 35 (19) ◽  
pp. 2125-2132 ◽  
Robert Chen ◽  
Pier Luigi Zinzani ◽  
Michelle A. Fanale ◽  
Philippe Armand ◽  
Nathalie A. Johnson ◽  

Purpose Hodgkin Reed-Sternberg cells harbor alterations in chromosome 9p24.1, leading to overexpression of programmed death-ligand 1 (PD-L1) and PD-L2. Pembrolizumab, a programmed death 1–blocking antibody, demonstrated a high overall response rate (ORR) in patients with relapsed or refractory classic Hodgkin lymphoma (rrHL) in phase I testing. Methods KEYNOTE-087 ( identifier, NCT02453594) was a single-arm phase II study of pembrolizumab in three cohorts of patients with rrHL, defined on the basis of lymphoma progression after (1) autologous stem cell transplantation (ASCT) and subsequent brentuximab vedotin (BV); (2) salvage chemotherapy and BV, and thus, ineligible for ASCT because of chemoresistant disease; and (3) ASCT, but without BV after transplantation. Patients received pembrolizumab 200 mg once every 3 weeks. Response was assessed every 12 weeks. The primary end points were ORR by central review and safety. Results A total of 210 patients were enrolled and treated (69 in cohort 1, 81 in cohort 2, and 60 in cohort 3). At the time of analysis, patients received a median of 13 treatment cycles. Per central review, the ORR was 69.0% (95% CI, 62.3% to 75.2%), and the complete response rate was 22.4% (95% CI, 16.9% to 28.6%). By cohort, ORRs were 73.9% for cohort 1, 64.2% for cohort 2, and 70.0% for cohort 3. Thirty-one patients had a response ≥ 6 months. The safety profile was largely consistent with previous pembrolizumab studies. Conclusion Pembrolizumab was associated with high response rates and an acceptable safety profile in patients with rrHL, offering a new treatment paradigm for this disease.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7530-7530
Sanjal Desai ◽  
Yucai Wang ◽  
Allison Claire Rosenthal ◽  
Craig B. Reeder ◽  
David James Inwards ◽  

7530 Background: Clinical trials of novel salvage therapies (ST) have encouraging outcomes for relapsed/refractory classic Hodgkin lymphoma (R/R cHL) eligible for autologous stem cell transplant (ASCT). In this observational study, we report efficacies and outcomes of different ST in ASCT-eligible R/R cHL. Methods: Consecutive ASCT-eligible R/R cHL pts at 3 Mayo Clinic sites were included. Demographics and clinical variables at relapse were recorded by medical records review. Time to event endpoints were defined from relapse. Univariate associations were confirmed in multivariate models of age, sex, B symptoms, stage, bulky disease (BD, single mass > 6 cm) extra nodal disease (END), primary refractory disease (PRD) and early relapse (ER, within 1 year). Results: From Jan 2008 to May 2020, 207 ASCT-eligible pts with R/R cHL were included. Median age was 33 (24-43) years, 53% were male, 52% had advanced stage, 24% had BD, 36% had B symptoms, 41% had END, 11% had PRD and 43% had ER. All patients received ST and underwent ASCT; 43 (21%) received 2 ST, 14 (7%) 3 ST and 4 (0.5%) received 4 ST. 6 groups of ST were identified: ifosfamide, carboplatin and etoposide (ICE), bendamustine/brentuximab (BBV), brentuximab vedotin (BV), gemcitabine-based therapy (Gem), checkpoint inhibitor (CPI), and others. Table lists response to first line ST. BBV had significantly higher overall response rate (ORR) and complete response (CR) as first ST in univariate and multivariate models. 114 (79%) after ICE, 30 (97%) after BBV, 15 (56%) after BV, 25 (76%) after Gem, 8 (73%) after CPI and 15 (79%) after other ST underwent ASCT. Higher number of pts were bridged to ASCT after BBV than ICE (p<0.01). 110 (53%) went to ASCT in CR, 74 (36%) in partial response (PR) and 11% in progressive disease (PD). 43 received BV maintenance (BVm) after ASCT. Pts going to ASCT in PR or PD had significantly lower progression free survival (PFS) compared to pts in CR (2 yr PFS: 62%, 18% vs 77%, respectively, p<0.0001) in univariate and multivariate models. There was no difference in PFS and overall survival (OS) by type of ST. BVm was associated with higher PFS (HR 0.3 (CI95 0.2-0.8)) and higher number of ST was associated with lower OS (HR 2 (CI95 1.4-3)) in multivariate model (p<0.001). For pts transplanted in CR, there was no significant difference in PFS and OS by type of ST but higher number of ST predicted lower OS (HR 2.4 (CI95 1.2-3.5), p<0.01). Conclusions: Type of ST did not predict survival, response to and number of ST did. For pts with CR, number of ST not type of ST predicted survival. BBV had higher response rates, higher rates of bridge to ASCT, and may be a preferable ST than ICE. Large, randomized trials are needed to evaluate efficacy of BBV compared to ICE.[Table: see text]

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 233-242 ◽  
Andrew M. Evens ◽  
Jordan Carter ◽  
Kah Poh Loh ◽  
Kevin A. David

Abstract Hodgkin lymphoma (HL) in older patients, commonly defined as ≥60 years of age, is a disease for which survival rates have historically been significantly lower compared with younger patients. Older HL patients appear to have different disease biology compared with younger patients, including increased incidence of mixed cellularity histology, Epstein-Barr virus–related, and advanced-stage disease. For prognostication, several studies have documented the significance of comorbidities and functional status in older HL patients, as well as the importance of achieving initial complete remission. Collectively, selection of therapy for older HL patients should be based in part on functional status, including pretreatment assessment of activities of daily living (ADL), comorbidities, and other geriatric measures (eg, cognition, social support). Treatment of fit older HL patients should be given with curative intent, regardless of disease stage. However, attention should be paid to serious treatment-related toxicities, including risk of treatment-related mortality. Although inclusion of anthracycline therapy is important, bleomycin-containing regimens (eg, doxorubicin, bleomycin, vinblastine, dacarbazine) may lead to prohibitive pulmonary toxicity, and intensive therapies (eg, bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) are too toxic. Brentuximab vedotin given sequentially before and after doxorubicin, vinblastine, and dacarbazine to fit, untreated advanced-stage older HL patients was recently shown to be tolerable and highly effective. Therapy for patients who are unfit or frail because of comorbidities and/or ADL loss is less clear and should be individualized with consideration of lower-intensity therapy, such as brentuximab vedotin with or without dacarbazine. Altogether, therapy for older HL patients should be tailored based upon a geriatric assessment, and novel targeted agents should continue to be integrated into treatment paradigms.

2016 ◽  
Vol 69 (1-2) ◽  
pp. 59-64
Dzemail Detanac ◽  
Dzenana Detanac ◽  
Avdo Ceranic ◽  
Merima Ceranic

Introduction. The aim of this study was to show the descriptive and histopathological analysis and applied surgical technique with early and late postoperative complications in patients with breast cancer who were hospitalized and treated at the General Hospital in Novi Pazar during the period 2009-2011. Material and Methods. During the period from 2009 to 2011, 59 patients were operated for breast cancer at the General Hospital in Novi Pazar. The study included the size and type of the tumor, disease stage, surgical techniques and complications, the age of the patients at the moment of surgery and its correlation with the number of metastatic lymph nodes in the axilla and the tumor size, as well as the correlation of the tumor size with the number of metastases in the axillary lymph nodes. Results. The difference in the tumor size in relation to the age among the women under 50 and over 50 years of age was not statistically significant (T = -1.203, p>0.05). There was no statistically significant difference between the number of positive lymph nodes in the women under and over 50 years of age (Mann-Whitney U test, p>0.05). A significant positive correlation between the tumor size and the number of positive axillary lymph nodes was found (r= 0.308, p<0.05). A significant positive correlation of the patient?s age and breast cancer stage was also confirmed with nonparametric variance analysis by Spearman?s Rho (r= 0.337, p<0.05). Conclusion. The majority of women from this study sample were with Stage II of breast cancer, which points out the necessity for better prevention and education of women in order to improve early diagnosis of breast cancer. The number of positive axillary lymph nodes appears to be an important prognostic factor and a significant positive correlation between the tumor size and the number of positive axillary lymph nodes has been found.

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