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

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.

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Long-term follow-up of the RESONATE phase 3 trial of ibrutinib vs ofatumumab

Blood ◽

10.1182/blood-2018-08-870238 ◽

2019 ◽

Vol 133 (19) ◽

pp. 2031-2042 ◽

Cited By ~ 62

Author(s):

John C. Byrd ◽

Peter Hillmen ◽

Susan O’Brien ◽

Jacqueline C. Barrientos ◽

Nishitha M. Reddy ◽

...

Keyword(s):

Single Agent ◽

The United States ◽

Lymphocytic Leukemia ◽

Baseline Risk ◽

Phase 3 ◽

Long Term Study ◽

Long Term Follow Up ◽

Over Time

Abstract Ibrutinib, a once-daily oral inhibitor of Bruton tyrosine kinase, has greatly improved outcomes for patients with chronic lymphocytic leukemia (CLL). The phase 3 RESONATE trial, which compared single-agent ibrutinib to ofatumumab in high-risk, relapsed patients with CLL, provided support for approval of ibrutinib in the United States and Europe. We describe long-term follow-up of patients treated in RESONATE, where continued superiority of progression-free survival (PFS) (hazard ratio [HR], 0.133; 95% confidence interval [CI], 0.099-0.178) was observed. Overall survival benefit continues (HR, 0.591; 95% CI, 0.378-0.926), although with decreased magnitude relative to that seen before crossover to ibrutinib was implemented for patients on ofatumumab (HR, 0.426; 95% CI, 0.220-0.823). Notably, overall response to ibrutinib increased over time, with 91% of patients attaining a response. The PFS benefit with ibrutinib was independent of baseline risk factors, although patients with ≥2 prior therapies had shorter PFS than those with <2 prior therapies, and the presence of TP53 or SF3B1 mutations showed a trend toward shorter PFS vs without these factors. Median duration of ibrutinib was 41 months, with 46% remaining on treatment at a median follow-up of 44 months. Grade ≥3 adverse events generally decreased over time, causing only a small proportion of patients to cease therapy. Ibrutinib was discontinued due to progressive disease in 27% of patients. This long-term study provides support for sustained efficacy and safety of ibrutinib in relapsed/refractory CLL and consideration of study provisions that allow crossover to investigational therapy when benefit has been clearly demonstrated. This trial was registered at www.clinicaltrials.gov as #NCT01578707.

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Six Cycles of BEACOPP Tailored Based on Interim Scintigraphy Provide Favorable Outcome for Patients with Standard and Advanced Risk Hodgkin Lymphoma and Female Fertility Is Preserved: Results of a 10-Year Follow-up

Blood ◽

10.1182/blood.v118.21.1564.1564 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1564-1564

Author(s):

Eldad J Dann ◽

Zeev Blumenfeld ◽

Rachel Bar-Shalom ◽

Irit Avivi ◽

Menachem Ben-Shachar ◽

...

Keyword(s):

Prognostic Factors ◽

Hodgkin Lymphoma ◽

Gnrh Agonist ◽

Ovarian Function ◽

Prognostic Score ◽

Individual Risk ◽

Term Survival ◽

Pet Ct

Abstract Abstract 1564 Background: Therapy of Hodgkin lymphoma (HL) is designed to prolong survival and minimize toxicity; however, an intense debate is ongoing over whether ABVD or BEACOPP should be used upfront and whether a long-term survival benefit is obtained with the BEACOPP regimen. The current study was aimed to personalize therapy based on individual risk factors and interim scintigraphy. Design and Methods: 124 patients with newly diagnosed HL and adverse prognostic factors were prospectively studied between 7/1999 and 8/2005. Patients with early unfavorable and advanced disease were eligible for the study. Study participants were assigned to therapy based on their International Prognostic Score (IPS). Those with an IPS of ≥3 were assigned to 2 cycles of escalated BEACOPP (EB). All others received 2 cycles of standard BEACOPP (SB). Subsequent therapy was prospectively allocated according to the results of early interim GA67 or PET/CT. Four cycles of EB or SB were administered following a positive or negative scan, respectively. Results: Complete remission (CR) rate, 10-year progression free (PFS) and overall survival (OS) were 97%, 87% and 88%, respectively, at a median follow-up of 89 months (5–144). Only 38% of patients, mostly with a bulky mediastinal mass, received radiation therapy. PFS and OS were similar in both groups. Predictive value of negative interim Ga67 or PET/CT was 87% and 93%, respectively. Fertility status was assessed in 38 females aged <40 years (Table). Twenty four of these patients received 6 cycles of SB, 8 patients had 2 cycles of EB and 4 cycles of SB, 3 patients were treated with 2 cycles of SB and 4 cycles of EB and one patient received 6 cycles of EB. Thirty six females did not have disease progression and 34 of them were found to preserve their cyclic ovarian function (COF). Twenty six females were co-treated with 6 cycles of GNRH agonist triptorelin (Decapeptyl 3.75 mg) for 6 months. 19 patients conceived during the follow-up (30 pregnancies), delivering 23 babies. Deliveries were reported for up to seven years from diagnosis. Notably, the female receiving 6 cycles of EB, co-administered with the GNRH agonist, was among those who conceived and delivered a healthy baby. Conclusion: Six cycles of tailored BEACOPP administered to HL patients with adverse prognostic factors provide encouraging long-term PFS and OS, and fertility is preserved in most females following reduction in the number of chemotherapy cycles and GNRH agonist co-administration. Disclosures: Off Label Use: GNRH agonist triptorelin was simultaneously administered for fertility preservation.

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Recurrence of Otitis Media after Antibiotic Therapy: Comparison of Cephradine and Amoxycillin

Journal of International Medical Research ◽

10.1177/030006057900700613 ◽

1979 ◽

Vol 7 (6) ◽

pp. 546-550 ◽

Cited By ~ 5

Author(s):

Samuel E McLinn

Keyword(s):

Side Effects ◽

Antibiotic Therapy ◽

Clinical Response ◽

Otitis Media ◽

Recurrence Rate ◽

Treatment Groups

The long-term effectiveness of cephradine and amoxycillin in the treatment of otitis media was evaluated in one hundred children ranging in age from 4 months to 14 years. The immediate clinical response was comparable in both treatment groups, but the recurrence rate during a 12-month follow-up period was considerably lower in the patients treated with cephradine. The incidence of side-effects was similar in the two groups.

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Long-Term Follow-up of 228 Hairy Cell Leukemia Patients Treated with Pentostatin or Cladribine with 15.4 Years Median Time from Diagnosis.

Blood ◽

10.1182/blood.v112.11.2101.2101 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2101-2101

Author(s):

Monica Else ◽

Claire E. Dearden ◽

Estella Matutes ◽

Ama Z S Rohatiner ◽

Steve A N Johnson ◽

...

Keyword(s):

Hairy Cell Leukemia ◽

Single Agent ◽

Second Line ◽

Hairy Cell ◽

Cell Leukemia ◽

First Line ◽

Treatment Groups ◽

Relapse Rates

Abstract Background: In a previous review of hairy cell leukemia (HCL) patients we found no difference in efficacy between cladribine and pentostatin [Else et al, Cancer 104:2442- 8; 2005]. With longer follow-up (median 15.4 years since diagnosis) we aimed to find whether efficacy remained equivalent and whether factors associated with relapse could be identified retrospectively. Methods: We reviewed data retrospectively from 228 HCL patients, treated between 1986–2005 with either single-agent pentostatin (n=187) or cladribine (n=41), at a median of 15.4 (range 1–38) years from diagnosis. Results: Patient demographics were similar for both treatment groups, apart from a male:female ratio of 4.5:1 (pentostatin) versus 2:1 (cladribine) (p=0.02). No statistically significant differences were found between treatment groups after first-line therapy. Complete response (CR) rates were 82% (pentostatin) and 76% (cladribine). After a median followup since treatment of 13 years (pentostatin) and 9 years (cladribine), 43% of pentostatin and 37% of cladribine patients had relapsed. Relapse rates at 5, 10 and 15 years were 25%, 42% and 47% (pentostatin) and 35%, 44% and 44% (cladribine). Overall, patients who reached 5 years remission had only a 30% risk of relapsing by 15 years. Median progression-free survival (PFS) was 10 years. After relapse (n=75) or non-response (n=5), 24 patients received single-agent pentostatin and 56 cladribine, with CR rates of 63% and 75% respectively (not significant). Eleven patients subsequently relapsed after pentostatin and 18 after cladribine. Ten years after second-line treatment the rate of relapse was 53% and 39% for the two agents respectively (not significant) and second-line PFS was marginally shorter after pentostatin than after cladribine (p=0.04). Relapse rates and PFS were no different between those switching treatment (n=51) and those re-treated with the same agent (n=29). There were 45 deaths altogether, of which only 8 were HCL-related. With non-HCL-related deaths censored, overall survival from first treatment was 95% (pentostatin) and 100% (cladribine) at both 10 and 15 years (not significant). Compared with all others, the 95 patients (42%) whose disease progressed (who failed to respond to treatment, relapsed, or died of HCL-related causes) were more likely to have haemoglobin <10g/dl (p=0.01) and platelets <100x109/l (p=0.002). The median first-line PFS of patients with haemoglobin <10g/dl and/or platelets <100x109/l was 8 years versus 16 years for all others (p<0.001). Conclusions and Recommendations: The long-term outcome for HCL patients was similar, whether treated with pentostatin or cladribine. The risk of dying of HCL-related causes was less than 5% and, among those surviving 15 years after treatment, 52% had still not relapsed. As in chronic lymphocytic leukaemia Binet stage C, patients with a low haemoglobin and/or platelet count appeared to fare worse. Further research will elucidate the factors underlying this difference in long-term prognosis. The outcome for relapsed patients may improve with the combination of either pentostatin or cladribine with the monoclonal antibody rituximab (Else et al, Cancer 110:2240–7; 2007).

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Self-reported paresthesias, Raynaud’s phenomena, tinnitus, and hearing impairment in a large cohort of long-term testicular cancer (TC) survivors

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.4547 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 4547-4547 ◽

Cited By ~ 2

Author(s):

M. Brydoy ◽

J. Oldenburg ◽

O. Klepp ◽

R. M. Bremnes ◽

E. Wist ◽

...

Keyword(s):

Logistic Regression ◽

Side Effects ◽

Well Being ◽

Cold Climate ◽

Treatment Groups ◽

Prior Therapy ◽

Separate Treatment ◽

In Cis

4547 Background: Persisting side-effects of treatment may impair the well-being of TC survivors. The aim of this study was to assess long-term Raynaud’s phenomena, oto-, and neurotoxicity related to prior therapy. Methods: A follow-up survey was conducted in men treated for TC 1980–1994 in Norway. The 1319 eligible responders had a median follow-up time of 11 years (range 4–21) and were allocated to four separate treatment groups: Surgery (Surg), Radiotherapy (Rt), and chemotherapy (Cisplatin [Cis] ≤ 850 mg and Cis > 850 mg). The questionnaire included six items assessing the relevant toxicities. The responders’ scores were dichotomized [minor (“not at all” or “a little”) vs. major (“quite a bit” or “very much”)] and analyzed by logistic regression with Surg as reference. Results: The proportion of cases (%) reporting major symptoms and the corresponding Odds ratios (OR) varied significantly between treatment groups ( table ). Rt was not statistically significantly different from Surg for any symptom, but showed a trend for higher scores of paresthesias in the feet. Cis > 850 mg differed significantly for all symptoms with major symptoms reported by 25–49% with the highest OR (8.1) for Raynaud’s phenomena in hands. Apart from Raynaud’s phenomena, paresthesias in feet were the only symptom significantly different in Cis < 850 mg compared to Surg. Conclusions: Toxicities induced by cisplatin-based chemotherapy persist in many TC survivors. A cold climate may contribute to the high perception of Raynaud’s phenomena in Norwegian TC survivors. [Table: see text] No significant financial relationships to disclose.

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

Blood ◽

10.1182/blood-2021-154354 ◽

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.

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Long-Term Follow-Up of Early Cochlear Implant Device Activation

Audiology and Neurotology ◽

10.1159/000512760 ◽

2021 ◽

pp. 1-11

Author(s):

Stefanie Bruschke ◽

Uwe Baumann ◽

Timo Stöver

Keyword(s):

Speech Recognition ◽

Side Effects ◽

Cochlear Implant ◽

Surgical Techniques ◽

Control Group ◽

First Year ◽

Safe Procedure ◽

Sound Processor

Background: The cochlear implant (CI) is a standard procedure for the treatment of patients with severe to profound hearing loss. In the past, a standard healing period of 3–6 weeks occurred after CI surgery before the sound processor was initially activated. Advancements of surgical techniques and instruments allow an earlier initial activation of the processor within 14 days after surgery. Objective: Evaluation of the early CI device activation after CI surgery within 14 days, comparison to the first activation after 4–6 weeks, and assessment of the feasibility and safety of the early fitting over a 12 month observation period were the objectives of this study. Method: In a prospective study, 127 patients scheduled for CI surgery were divided into early fitting group (EF, n = 67) and control group (CG, n = 60). Individual questionnaires were used to evaluate medical and technical outcomes of the EF. Medical side effects, speech recognition, and follow-up effort were compared with the CG within the first year after CI surgery. Results: The early fitting was feasible in 97% of the EF patients. In the EF, the processor was activated 25 days earlier than in the CG. No major complications were observed in either group. At the follow-up appointments, side effects such as pain and balance problems occurred with comparable frequency in both groups. At initial fitting, the EF showed a significantly higher incidence of medical minor complications (p < 0.05). When developing speech recognition within the first year of CI use, no difference was observed. Furthermore, the follow-up effort within the first year after CI surgery was comparable in both groups. Conclusions: Early fitting of the sound processor is a feasible and safe procedure with comparable follow-up effort. Although more early minor complications were observed in the EF, there were no long-term wound healing problems caused by the early fitting. Regular inspection of the magnet strength is recommended as part of the CI follow-up since postoperative wound swelling must be expected. The early fitting procedure enabled a clear reduction in the waiting time between CI surgery and initial sound processor activation.

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Physiological Pacing: A New Road to Future

Indian Journal of Clinical Cardiology ◽

10.1177/2632463620978045 ◽

2021 ◽

pp. 263246362097804

Author(s):

Vanita Arora ◽

Pawan Suri

Keyword(s):

Side Effects ◽

Fibrous Tissue ◽

Cardiac Pacing ◽

His Bundle ◽

Anatomy And Physiology ◽

Long Term Follow Up ◽

Pacing Lead ◽

The Right

Anatomy and physiology are the basis of human body functioning and as we have progressed in management of various diseases, we have understood that physiological intervention is always better than an anatomical one. For more than 50 years, a standard approach to permanent cardiac pacing has been an anatomical placement of transvenous pacing lead at the right ventricular apex with a proven benefit of restoring the rhythm. However, the resultant ventricular dyssynchrony on the long-term follow-up in patients requiring more than 40% ventricular pacing led to untoward side effects in the form of heart failure and arrhythmias. To counter such adverse side effects, a need for physiological cardiac pacing wherein the electrical impulse be transmitted directly through the normal conduction system was sought. His bundle pacing (HBP) with an intriguing alternative of left bundle branch pacing (LBBP) is aimed at restoring such physiological activation of ventricles. HBP is safe, efficacious, and feasible; however, localization and placement of a pacing lead at the His bundle is challenging with existing transvenous systems due to its small anatomic size, surrounding fibrous tissue, long-learning curve, and the concern remains about lead dislodgement and progressive electrical block distal to the HBP lead. In this article, we aim to take the reader through the challenging journey of HBP with focus upon the hardware and technique, selective versus nonselective HBP, indications and potential disadvantages, and finally the future prospects.

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