scholarly journals Single-Agent Rituximab and Ultra-Low-Dose Adaptive Radiotherapy for the Treatment of Indolent Non-Hodgkin Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4510-4510
Author(s):  
Meredith Jackson ◽  
Sean All ◽  
Samantha Brocklehurst ◽  
Neil B Desai ◽  
Jennifer L Shah ◽  
...  
Keyword(s):  
Disease Control ◽  
Hodgkin Lymphoma ◽  
Local Control ◽  
Low Dose ◽  
Single Agent ◽  
Combined Modality Treatment ◽  
Overall Response ◽  
Non Hodgkin Lymphoma

Abstract Introduction For indolent non-Hodgkin lymphoma (NHL), there is level 1 evidence (FoRT) demonstrating superior long term local control with 24 Gy radiation treatment (RT) over ultra-low-dose 4 Gy RT (Hoskin et al Lancet 2021). However, it's notable that over 2/3 of those receiving ultra-low-dose RT did achieve durable local control. Further, with RT alone to any dose, the predominant pattern of failure is distal. Thus, the TROG study showed that the addition of systemic therapy (rituximab, cyclophosphamide, vincristine) after RT (30 Gy) significantly improved progression free survival (PFS). However, cytotoxic chemotherapy and higher dose RT can both cause significant, and potentially unnecessary, toxicities. We hypothesize that for indolent NHL, the combination of single-agent rituximab and ultra-low-dose adaptive RT, with repeat treatment as needed, will result in excellent local and systemic disease control with minimal toxicities. Methods We conducted an IRB approved, retrospective review of patients with indolent NHL who were treated with both ultra-low-dose RT (2 Gy x 2 or "boom boom") and single-agent rituximab (4 cycles) either concurrently or within a short interval (median 13 days) at our institution from 2017-2020. 17 treatments [follicular (9), marginal zone (4), mucosal associated lymphoid tissue (3), other (1)] from 15 patients were identified. Treatment sites included pelvis (5), parotid (4), abdomen (4), mediastinum (1), and other (3). The median ECOG performance status was 1 (range: 0-2), the median age was 74 (range: 25-90), and 9/15 patients were male. 7 patients were stage I, 5 stage II, 2 stage III, and 1 stage IV. 3 patients had prior RT with 1 patient having the same spot irradiated twice, and the other 2 both having RT at 2 distal sites. Only 1 patient had prior systemic treatment (ibrutinib) for their low-grade lymphoma. The primary outcomes were rates of complete response (CR), partial response (PR), overall response (defined as CR or PR), stable disease (SD), or progressive disease (PD). Secondary outcomes included PFS, overall survival (OS), symptom relief, and acute and long-term toxicities. Radiographic studies (predominantly PET/CT) were used to determine treatment response and disease control. Results In our cohort with median follow up of 16 months, the PFS and OS at one year was 93% (14/15)and 100% (15/15), respectively. The overall response rate was 94% (16/17), of which 13 sites (76%) achieved CR, 3 (18%) had PR, and 1 (6%) had SD. Of those with PR, 1 had residual disease in the field of RT, 1 outside the field of RT, and 1 both in and out of the field of RT. For the first 2, repeat ultra-low-dose RT was given to sites of PR and both achieved CR. The remaining patient with both in and out of field PR was managed with active surveillance with SD on last follow up. 2 patients experienced acute toxicities, 1 with mild diarrhea from pre-sacral RT that resolved within days, and 1 with dysgeusia from parotid RT that resolved within 2 months. Only 1 patient noted long-term toxicity of dry mouth with about 50% reduction in saliva after left parotid gland RT, but of note this patient also had preexisting Sjogren's syndrome. Symptoms were present in 10 patients, of which 9 noted improvement after treatment. The only patient whose symptoms did not improve was the patient with SD. This patient had neuro involvement of the lymphoma with multiple confounding factors. Conclusion Combined modality treatment with single-agent rituximab and ultra-low-dose adaptive RT, with retreatment as needed, in patients with indolent NHL appears to provide effective palliation and disease control with minimal toxicity. For patients with concerns for radiation or chemotherapy related toxicity, this presents an attractive alternate treatment paradigm that warrants further evaluation in larger prospective studies. Disclosures Desai: Boston Scientific: Consultancy, Research Funding. Awan: ADCT therapeutics: Consultancy; Cardinal Health: Consultancy; Merck: Consultancy; BMS: Consultancy; Dava Oncology: Consultancy; Johnson and Johnson: Consultancy; Beigene: Consultancy; Incyte: Consultancy; Verastem: Consultancy; MEI Pharma: Consultancy; Karyopharm: Consultancy; Celgene: Consultancy; Kite pharma: Consultancy; Gilead sciences: Consultancy; Pharmacyclics: Consultancy; Janssen: Consultancy; Abbvie: Consultancy; Astrazeneca: Consultancy; Genentech: Consultancy.

scholarly journals Combined Modality Low-Dose Radiation Therapy (2 Gy x 2) and Single-Agent Rituximab Immunotherapy in the Treatment of Indolent Non-Hodgkin Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5262-5262
Author(s):  
Samantha Brocklehurst ◽  
Neil Desai ◽  
Jennifer L Shah ◽  
Syed Rizvi ◽  
Praveen Ramakrishnan Geethakumari ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Disease Control ◽  
Low Dose ◽  
Response Rate ◽  
Single Agent ◽  
Progression Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Progression Of Disease

Introduction Low-dose involved site radiation therapy (ISRT) of 2 Gy x 2 is effective in terms of palliation and local control for indolent Non-Hodgkin Lymphoma (NHL), with >80% response rate (Hoskin et al., Lancet 2014). It is commonly used in patients for whom radiation-related toxicity is of concern due to location, volume of disease, or poor performance status, and because of the ease of re-treatment if necessary. An alternative treatment for these patients is rituximab monotherapy, which is well-tolerated and has a good initial response rate but poor long-term response rate (Ardeshna et al., Lancet 2014). To date, no study has examined the efficacy of low-dose ISRT with single-agent rituximab in patients for whom treatment-related toxicity is a concern. We hypothesize that this combination is an effective treatment modality for indolent NHL that may result in the optimal balance of local and systemic disease control with minimal toxicity. Methods From a prospectively maintained clinical database of patients treated with radiation therapy (RT) at UT-Southwestern Medical Center, we performed an IRB-approved, retrospective review of 40 treated sites from 34 patients with indolent B-cell lymphoma (predominantly follicular, marginal zone, and mucosal associated lymphoid tissue) treated with low-dose ISRT (2 Gy x 2) between 2013-2019. Of primary interest, 7 patients received single-agent rituximab (median 4 cycles) either concurrently or within a short interval (median 18 days) of their ISRT, with a median follow-up of 13 months. Of the remaining patients, 14 received RT alone and 13 received combination therapy (predominantly bendamustine-rituximab or R-CHOP). Of the patients who received a combination of low-dose ISRT and single-agent rituximab, treated sites included parotid (3), brain (2), orbit (1), and pre-sacral space (1). The median ECOGperformance status was 1 (range, 1-2), the median age was 75 (range, 21-87), and 4/7 patients were female. The majority of patients were stage I (5), and remaining were stage II (1) and stage III (1). Nopatients had prior RT or systemic therapies. The primary outcome was response rate, categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD).Secondary outcomes included progression free survival (PFS), overall survival (OS), symptom relief, and acute and long-term toxicities. Treatment response and disease control were determined by radiographic studies and/or physical examinations. SPSS Statistics software was used for statistical analysis. Results In all patients who received low-dose ISRT, the progression-free survival and overall survival at 1-year was 58% and 82%, respectively. In the patients who received combined low-dose ISRT and single-agent rituximab, the response rate was 100% (7/7), of which 5 had CR, 1 had PR and 1 had SD at the time of latest follow-up. For patients with multiple lesions (stage II-III), there was a 100% CR rate of un-irradiated lesions as well. There were no distal failures or deaths. Of note, 1 patient had progression of disease locally and a second had progression of disease distally initially after ISRT, both of which resolved as SD and CR, respectively, after the administration of rituximab. Also, 1 patient had progression of disease locally while receiving rituximab maintenance therapy, which resolved as CR after treatment with ISRT. Two patients experienced acute toxicities, 1 with mild diarrhea from presacral RT that resolved within days and 1 with dysgeusia from parotid RT that resolved within 2 months. Only 1 patient noted long-term toxicity from RT, in the form of dry mouth from about 50% reduction in saliva post-RT to the left parotid gland. All 7 patients presented with symptoms, of which 6 noted improvement. The remaining 1 patient had stable symptoms, as well as SD, with significant improvement in her initial condition confounded by a lower presenting ECOG and C2 fracture from a symptomatic fall prior to RT. Conclusion In patients with indolent lymphoma, combined low-dose ISRT of 2 Gy x 2 with single-agent rituximab appears to provide effective palliation and disease control with minimal toxicity. This combination is a promising new treatment paradigm, particularly for patients in whom radiation or chemotherapy related toxicities are of concern, and warrants evaluation in a larger prospective series. Disclosures No relevant conflicts of interest to declare.

scholarly journals Rituximab-Containing Risk-Adapted Treatment Strategy in Nodular Lymphocyte Predominant Hodgkin Lymphoma: 7-Years Follow-Up

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1760
Author(s):  
Novella Pugliese ◽  
Marco Picardi ◽  
Roberta Della Pepa ◽  
Claudia Giordano ◽  
Francesco Muriano ◽  
...  
Keyword(s):  
Side Effects ◽  
Hodgkin Lymphoma ◽  
Prognostic Score ◽  
Single Agent ◽  
Response To Therapy ◽  
Baseline Risk ◽  
Historical Cohort ◽  
Treatment Groups

Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare variant of HL that accounts for 5% of all HL cases. The expression of CD20 on neoplastic lymphocytes provides a suitable target for novel treatments based on Rituximab. Due to its rarity, consolidated and widely accepted treatment guidelines are still lacking for this disease. Methods: Between 1 December 2007 and 28 February 2018, sixteen consecutive newly diagnosed adult patients with NLPHL received Rituximab (induction ± maintenance)-based therapy, according to the baseline risk of German Hodgkin Study Group prognostic score system. The treatment efficacy and safety of the Rituximab-group were compared to those of a historical cohort of 12 patients with NLPHL who received Doxorubicin, Bleomycin, Vinblastine, Dacarbazine (ABVD) chemotherapy followed by radiotherapy (RT), if needed, according to a similar baseline risk. The primary outcome was progression-free survival (PFS) and secondary outcomes were overall survival (OS) and side-effects (according to the Common Terminology Criteria for Adverse Events, v4.03). Results: After a 7-year follow-up (range, 1–11 years), PFS was 100% for patients treated with the Rituximab-containing regimen versus 66% for patients of the historical cohort (p = 0.036). Four patients in the latter group showed insufficient response to therapy. The PFS for early favorable and early unfavorable NLPHLs was similar between treatment groups, while a better PFS was recorded for advanced-stages treated with the Rituximab-containing regimen. The OS was similar for the two treatment groups. Short- and long-term side-effects were more frequently observed in the historical cohort. Grade ≥3 neutropenia was more frequent in the historical cohort compared with the Rituximab-group (58.3% vs. 18.7%, respectively; p = 0.03). Long-term non-hematological toxicities were observed more frequently in the historical cohort. Conclusion: Our results confirm the value of Rituximab in NLPHL therapy and show that Rituximab (single-agent) induction and maintenance in a limited-stage, or Rituximab with ABVD only in the presence of risk factors, give excellent results while sparing cytotoxic agent- and/or RT-related damage. Furthermore, Rituximab inclusion in advanced-stage therapeutic strategy seems to improve PFS compared to conventional chemo-radiotherapy.

scholarly journals Axicabtagene Ciloleucel (axi-cel; KTE-C19) in Patients with Refractory Aggressive Non-Hodgkin Lymphoma (NHL): Long-Term Follow-up of the Pivotal Zuma-1 Trial

2018 ◽  
Vol 24 (3) ◽  
pp. S74-S75 ◽  
Author(s):  
Sattva S. Neelapu ◽  
Frederick L. Locke ◽  
Nancy L. Bartlett ◽  
Lazaros J. Lekakis ◽  
David Miklos ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Non Hodgkin Lymphoma ◽  
Long Term Follow Up

Subcutaneous epcoritamab in patients with relapsed/refractory B-cell non-Hodgkin lymphoma: Safety profile and antitumor activity.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7518-7518
Author(s):  
Michael Roost Clausen ◽  
Pieternella Lugtenburg ◽  
Martin Hutchings ◽  
Peter W. M. Johnson ◽  
Kim M. Linton ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Safety Profile ◽  
Cell Lymphoma ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
Non Hodgkin Lymphoma ◽  
Grade 3

7518 Background: Epcoritamab is a CD20xCD3 bispecific antibody that induces T-cell–mediated killing of CD20–positive malignant B-cells. We present updated data, including progression-free survival (PFS) from the dose escalation part of the first-in-human phase 1/2 study of epcoritamab in pts with relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL; NCT03625037). Methods: Adults with R/R CD20+ B-NHL received flat-dose 1 mL SC epcoritamab (step-up dosing approach) in 28-day cycles (q1w: cycles 1–2; q2w: cycles 3–6; q4w thereafter) until disease progression or unacceptable toxicity. Step-up dosing and standard prophylaxis were used to mitigate severity of cytokine release syndrome (CRS). Results: At data cut off (1/31/2021), 68 pts with B-NHL were enrolled across histologies including diffuse large B-cell lymphoma (DLBCL; n = 46 [67.6%]; de novo and transformed), follicular lymphoma (FL; 12 [17.6%]), mantle cell lymphoma (MCL; 4 [5.9%]), and others (6 [8.8%]). Majority were heavily pretreated (median [range] prior lines: DLBCL, 3 [1–6]; FL, 4.5 [1–18]); including prior CAR-T (n = 6) and prior ASCT (n = 10). At median follow-up of 14.1 mo (DLBCL, 10.2 mo; FL, 15.2 mo), treatment was ongoing in 15 (22%) pts. Most common treatment-emergent adverse events (AEs) were pyrexia (69%), CRS (59%), and injection site reaction (47%). CRS events were all grade 1 or 2 and most occurred in cycle 1; neurotoxicity was limited (6%; grade 1: 3%; grade 3: 3%; all transient). One case of tumor lysis syndrome was observed (1.5%; grade 3); there were no cases of febrile neutropenia or treatment-related death. Overall response is shown for DLBCL ≥12 mg and ≥48 mg and FL ≥12 mg, corresponding to the minimal efficacy threshold (Table). Responses deepened over time (PR converted to CR: DLBCL, 6 pts; FL, 3 pts). Median time to response was 1.4 mo (DLBCL) and 1.9 mo (FL). Among DLBCL pts achieving CR with ≥6 mg (n = 11), none relapsed while on treatment. The median PFS for pts with DLBCL ≥12 mg (n = 22) was 9.1 mo (95% CI: 1.6, NE; median follow-up 9.3 mo) and for pts with DLBCL ≥48 mg (n = 11) median PFS was not reached (median follow-up 8.8 mo). Updated analyses will be presented. Conclusions: With longer follow-up, SC epcoritamab demonstrated substantial single-agent activity, inducing deep and durable clinically meaningful responses, with a consistent safety profile. Notably no severe (grade ≥3) CRS events, no febrile neutropenia, and limited neurotoxicity was observed. Clinical trial information: NCT03625037. [Table: see text]

Responses to Thalidomide Combined with Prednisone Therapy for Myelofibrosis with Myeloid Metaplasia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3623-3623
Author(s):  
Shenxian Qian ◽  
Junfeng Tan ◽  
Pengfei Shi ◽  
Gaqian Gao
Keyword(s):  
Bone Marrow ◽  
Low Dose ◽  
Single Agent ◽  
Drug Effects ◽  
Myeloid Metaplasia ◽  
Baseline Status ◽  
Myelofibrosis With Myeloid Metaplasia ◽  
Sequential Phase

Abstract Myelofibrosis with myeloid metaplasia (MMM) is currently classified as a classic (i.e. not yet molecularly defined) myeloproliferative disorder (MPD), along with essential thrombocythemia (ET) and polycythemia vera (PV). All three MPDs represent stem-cell-derived clonal myeloproliferation that, in the case of MMM, is accompanied by an intense bone marrow stromal reaction that includes collagen fibrosis, osteosclerosis, and angiogenesis. To present the results of a long-term analysis of 2 sequential phase 2 trials of thalidomide (alone or in combination) for palliation of myelofibrosis with myeloid metaplasia (MMM). We analyzed (March 2003 to August 2005) initial and long-term outcomes from 33 patients with symptomatic MMM who had enrolled in either our thalidomide single-agent trial (n=12) or our trial of low-dose thalidomide (50 mg/d) combined with prednisone (n=21). Among the 33 study patients, 18 (54%) showed some improvement in their clinical course. Response rates for specific end points included improvements in anemia (12 of 33 [36%]), thrombocytopenia (8 of 12 [66%]), or splenomegaly (5 of 30 [17%]). The combination of low-dose thalidomide and prednisone, as opposed to single-agent thalidomide, was better tolerated and more efficacious. After a median follow-up of 17 months (range, 9–27 months), 10 of 33 patients (33%) showed an ongoing response, including 8 patients in whom protocol treatment has been discontinued for a median of 21 months (range, 16–27 months). Durable treatment responses were documented for only anemia and thrombocytopenia. Treatment response was not affected by the baseline status of bone marrow fibrosis, angiogenesis, osteosclerosis, cytogenetics. Unusual drug effects, all reversible, included leukocytosis (8 patients) and/or thrombocytosis (6 patients). Thalidomide (alone or combined with prednisone) is an effective first-line treatment of symptomatic anemia or thrombocytopenia in MMM. Thalidomide-based therapy has the potential to produce durable responses in MMM-associated cytopenias, even after discontinuation of the drug.

scholarly journals OUTCOME AND TOXICITY PATTERNS IN CHILDREN AND ADOLESCENTS WITH NON-HODGKIN LYMPHOMA: A SINGLE INSTITUTION EXPERIENCE

2018 ◽  
Vol 10 (1) ◽  
pp. e2018020 ◽  
Author(s):  
Paola Angelini ◽  
Laura Rodriguez ◽  
Mohammed Zolaly ◽  
Ahmed Naqvi ◽  
Sheila Weitzman ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Hodgkin Lymphoma ◽  
Survival Rates ◽  
Age At Diagnosis ◽  
Single Institution ◽  
Non Hodgkin Lymphoma ◽  
Sick Children ◽  
The Impact

Background: The incidence and biology of non-Hodgkin lymphoma (NHL) vary according to age. Some data suggest that the impact of age in pediatric and adolescent NHL patients depends on the histological subtype. Objectives: We aimed to analyze the impact of age at diagnosis on clinical characteristics and treatment-related toxicity in children and adolescents with NHL.Methods: Retrospective review of medical records of children and adolescents diagnosed with NHL at the Hospital for Sick children, Toronto, between January 1995 and December 2008.Results: 164 children were diagnosed with NHL during the study period, with a median age at diagnosis of 10 years. With a median follow-up of 6.2 years, 5-year OS in patients aged <15 and 15-18 years was 89± 2% vs 82% ± 6%, respectively (P = 0.30), and 5-year EFS was 84% ± 3% vs. 77% ± 7%  (P= 0.37). In Burkitts lymphoma (BL) and lymphoblastic lymphoma (LL) there was a trend towards better outcomes in children compared to adolescents, with EFS of  91% ± 4% vs. 75% ± 15%, respectively in BL (P= 0.17),  and 82% ± 7% vs. 51.4% ± 2% respectively in LL (P= 0.16). Late effects occurred in 21 patients (12.8%).Conclusions: Children with NHL aged < 15 years tend to have better survival rates and less long-term toxicity than adolescents aged 15-18 years.

Contemporary Management of Jugular Paragangliomas With Neural Preservation

2020 ◽  
pp. 019459982093866
Author(s):  
Nauman F. Manzoor ◽  
Kristen L. Yancey ◽  
Joseph M. Aulino ◽  
Alexander D. Sherry ◽  
Mohamed H. Khattab ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Local Control ◽  
Radiation Treatment ◽  
Tumor Control ◽  
Subtotal Resection ◽  
Combined Modality Treatment ◽  
Single Predictor ◽  
Jugular Paragangliomas

Objectives Management of jugular paragangliomas (PGL) has evolved toward subtotal resection (STR). The purpose of this study is to analyze neural preservation and adjuvant treatment for long-term local control. Study Design Retrospective chart review. Settings Tertiary neurotology practice. Subjects and Methods Adults undergoing surgical treatment of jugular PGL between 2006 and 2019. Patients, disease, and treatment variables were collected retrospectively. Single predictor logistic regression was used to ascertain predictors of regrowth or need for salvage radiation. Results A total of 41 patients (median age, 47 years; 76% female) were identified. Most patients presented with advanced-stage disease (Glasscock-Jackson stage III-IV = 76%). Subtotal resection (STR) was performed in 32 (78%) patients. Extended STR (type 1) was the most commonly performed conservative procedure (n = 19, 59%). Postoperative new low cranial neuropathy (LCN) involving CN X and XII was rare (n = 3 and n = 1, respectively). Seventeen patients (41%) underwent postsurgical therapy for tumor regrowth or recurrence, including 15 patients who underwent adjuvant (n = 4) or salvage (n = 11) radiation. Overall tumor control of 94.7% was achieved at a mean follow-up of 35 months. All patients treated with combined modality treatment had local control at last follow-up. Logistic regression identified no single predictor for postsurgical radiation treatment or salvage-free survival. Conclusion Management of jugular PGL with a conservative approach is safe and effective with a low rate of new LCN deficit. Active surveillance of residual tumor with salvage radiation for growth results in excellent long-term tumor control.

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