194 A multicenter characterization of chronic toxicities following adjuvant anti-PD-1 therapy for high risk resected melanoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A209-A209
Author(s):  
James Patrinely ◽  
Rebecca Johnson ◽  
Aleigha Lawless ◽  
Prachi Bhave ◽  
Amelia Sawyers ◽  
...  

BackgroundAnti-programmed death-1 (anti-PD-1) therapies have improved long-term survival across many advanced cancers. However, chronic immune-related adverse events (irAEs) are not well-defined. We sought to determine the incidence, time-course, spectrum, and predictors of chronic irAEs arising from adjuvant anti-PD-1.MethodsIn this retrospective cohort, we analyzed patients from 8 academic medical centers with stage III-IV melanoma treated with anti-PD-1 in the adjuvant setting. Acute and chronic (persisting at least 3 months after therapy cessation) irAEs were characterized by type, time-course, management, and incidence.ResultsAmong 387 patients, most were male (60.7%) with a median age of 63 years, had cutaneous primaries (85.8%), BRAF/NRAS WT (51.2%), and resected stage IIIb (33.1%) or IIIc (39.5%) melanomas. Median overall survival and relapse-free survival (RFS) were not reached. 359 patients (93.0%) were alive at median follow-up of 529 days. Patients with acute (p<0.009) or chronic (p<0.001) irAEs had superior RFS compared with patients lacking irAEs. Treatment was discontinued for therapy completion (50.0%), irAEs (25.3%), and disease progression (20.9%). 267 patients (69.0%) had any acute irAE, including 19.5% (n=52) with grade 3–5 events. Acute irAEs were most commonly dermatitis/pruritis (25.8%), thyroiditis/hypothyroid (16.3%), arthralgias (10.6%), colitis/diarrhea (9.8%) and required glucocorticoids in 109 patients (28.2%). Of these, 167 patients (43.2%) developed chronic irAEs; 82 (49.1%) were symptomatic, 55 (32.9%) required glucocorticoids, and most were grade 1–2 (96.4%). Endocrinopathies (73/88, 83.0%) arthritis (22/45, 48.9%), xerostomia (9/17, 52.9%), neurotoxicities (8/8, 100.0%), and ocular events (5/8, 63.0%) were likely to become chronic events. In contrast, colitis (6/44, 13.6%), hepatitis (4/25, 16.0%), pneumonitis (6/18, 33.3%) were less likely to become chronic. Overall, the most common chronic irAEs were hypothyroidism (14.0%), dermatitis/pruritis (6.6%) arthralgias (5.7%), adrenal insufficiency (3.1%), and xerostomia (2.3%). Age (p=0.67), gender (p=0.31), time of onset of acute irAEs (p=0.95), and initial need for glucocorticoids (p=0.15) were not associated with chronicity. Only 24 (14.4%) of chronic irAEs ultimately resolved during the median 529-day follow-up. In particular, endocrinopathies (100%) arthralgias (100%) ocular events (100%), xerostomia (88.9%), and cutaneous events (89.5%) had high rates of persistence at last follow-up.ConclusionsChronic irAEs to anti-PD-1 were more common than previously recognized and frequently persisted even with prolonged follow-up, although most were low-grade. The risks of chronic toxic effects should be integrated into treatment decision making.Ethics ApprovalThis study was approved by the Vanderbilt Institutional Review Board

1994 ◽  
Vol 80 (1) ◽  
pp. 20-25 ◽  
Author(s):  
Michael S. B. Edwards ◽  
William M. Wara ◽  
Samuel F. Ciricillo ◽  
A. James Barkovich

✓ Six children with a history of isolated facial nerve dysfunction or dizziness and nausea were treated for brain-stem glioma between 1984 and 1992. Computerized tomography and/or magnetic resonance (MR) imaging showed a focal, uniformly enhancing mass involving the facial nerve nucleus of the pons. All patients underwent biopsy; the histological diagnosis was juvenile pilocytic astrocytoma in five cases. In the remaining case the biopsy was nondiagnostic, although the surgeon believed that the lesion was a glioma. Postoperatively, five patients underwent conventional focal megavoltage radiation therapy (180 to 200 cGy/day) over a period of 5½ weeks to a total dose of approximately 5400 cGy. One child's family refused radiation therapy; she remained well and stable for 4 years, despite persistent facial weakness, and was eventually lost to follow-up review. Four irradiation-treated patients had complete resolution of their tumors on MR images and have had no evidence of neuropsychological or neuroendocrinological deficits during 4½ to 8 years of follow-up evaluation. Patients whose neuroradiological studies show a lesion resembling those in this series should undergo biopsy and, if the histology of a low-grade tumor (in particular, a juvenile pilocytic astrocytoma) is confirmed, should then receive focal radiation therapy with conventional megavoltage dosages.


2010 ◽  
Vol 2 (2) ◽  
pp. 97-100
Author(s):  
Gregory W Randolph ◽  
Carrie C Lubitz ◽  
William C Faquin ◽  
Randall D Gaz ◽  
Parangi Sareh ◽  
...  

Abstract Objective To report a case of melanoma metastatic to the thyroid gland and to review our experience with secondary neoplasms of the thyroid. Methods We depict the presentation and treatment of the patient, illustrating pathologic and radiologic findings. All patients with pathologic confirmation of metastatic tumors of the thyroid undergoing thyroidectomy at the Massachusetts General Hospital were reviewed (1995- 2008). Results A 59-year-old male presented with malignant melanoma of the scalp. Two months following his melanoma excision and lymphadenectomy, he underwent a hemi-thyroidectomy for fine-needle aspirate positive solitary metastasis. He initially did well, but on follow-up was noted to have diffuse metastases and expired from his disease eight months following initial diagnosis. Institutional review revealed 13 additional patients with pathologically confirmed secondary thyroid tumors. Conclusions FNA remains an indispensable diagnostic tool. Palliation from local compressive symptoms is an indication for surgery and long-term survival is seen in some patients undergoing resection of isolated metastases.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4665-4665
Author(s):  
Severiano Baltazar-Arellano ◽  
Patricia Pimentel ◽  
Luis Vera ◽  
Fernando Bezares ◽  
Jose Málaga ◽  
...  

Abstract Background: fludarabine (F) is licensed for the management of indolent non Hodgkin’s lymphoma in countries such as Canada and Switzerland. Clinical evidence suggests that fludarabine monotherapy is as least as effective, than conventional therapies such as cyclophosphamide, vincristine, prednisone (CVP) for the first and second line treatment of B-cell low grade NHL achieving objective response rates. Better response rates can be achieved combining F with Mitoxantrone (M) in low grade NHL even in refractory relapsed (RR) patients (pts). The Latin American Cooperative Oncology Hematology Group (LACOHG) proposed a multicenter study in Latin American countries in 2002 to use FM in RR B-cell low grade NHL. Aims: to assess the response rate, safety, disease free survival (DFS) and overall survival (OS) of FM in RR B-cell low grade NHL during (2003–2006). Methods: Forty-eight patients in the period of January 2003 to February 2006 were evaluated. Forty-four pts. had follicular lymphoma and 4 small lymphocytic lymphoma. Median age 63.5 years old (range: 24–83). Gender: female 56% and male 44%. Inclusion criteria for low grade NHL-LG was: any previous treatment excluding autologous transplantation, Ann Arbor stage II to IV, age &gt; 18 years old, ECOG performance status 0–2 and written informed consent. ECOG performance status 0: 2%, 1: 71% and 2: 27%. Ann Arbor staging: II: 2%, III: 29% and IV: 69%. International Prognostic Index (IPI): 0–1: 19%, 2–3: 71% and 4–5: 10%. Median previous treatment was 1 (range: 1–3). FM treatment consisted of F 25 mg/m2 i.v. (day 1–3) and M 10 mg/m m2 i.v. (day 1) each 28 days for 6–8 cycles. Results: on this low grade NHL cohort the overall response rate (ORR was 81%; progressive disease and non-response 19%. With a median follow up of 17 months, OS at 24 months was 86% (DE 5.2%) and DFS at 24 months 57.1% (DE 11.3%). LDH in serum was not an adverse prognostic factor for DFS and OS. Safety: on the 286 cycles in 48 pts, the toxicity was: 18 episodes of grade 3-4 neutropenias, 15 episodes of grade 3-4 thrombocytopenia, 7 episodes of grade 1–2 nausea/vomiting, grade 1–2 diarrhea in 4 pts, 8 pts were admitted to the clinic, 11 fever episodes, 2 allopecia, 4 pts developed grade 1–2 peripheral neuropathy and infections 7%: one case herpes zoster. Mortality rate: 12,5% (6/48 patients), 5 of them because progressive disease. No cardiac toxicity was reported. Conclusions: FM is an effective and safe treatment for RR low grade NHL. A longer follow up and a larger trial, might be needed to confirm these results in a multicenter, randomized study. DFS with FM in RR low grade NHL : LACOHG DFS with FM in RR low grade NHL : LACOHG


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 858-858 ◽  
Author(s):  
David A. Rizzieri ◽  
Jeffrey L Johnson ◽  
John C. Byrd ◽  
Gerard Lozanski ◽  
Bayard L. Powell ◽  
...  

Abstract Abstract 858 Prior studies have shown that combination chemotherapy using high doses of antimetabolites and alkylating agents over a short duration is effective treatment for Burkitt leukemia and lymphoma. Adults able to tolerate this therapy have had > 50% long term survival, although those with higher risk by the International Prognostic Index (IPI) have had inferior outcomes. Between 5/2002 and 9/2009, we enrolled 105 adults (19-79 yrs old) with untreated Burkitt leukemia/lymphoma onto a phase II study of a high intensity chemo-immunotherapy regimen to assess the benefit of adding rituximab plus growth factor support to the intensive chemotherapy regimen developed in CALGB 9251 and evaluated patterns of relapse when prophylactic cranial irradiation was not given. All subjects were HIV negative and had serum creatinine and bilirubin ≤1.5 × upper limit. Complete data are available on 105 patients for toxicity and 103 patients for efficacy. Methods: Treatment began with cyclophosphamide (CY) 200 mg/m2 × 5 days and prednisone 60 mg/m2 × 7 days. Cycle 2 was started on Day 8 after entry. Cycles 2, 4, and 6 consisted of ifosfamide 800 mg/m2 on days 1–5, methotrexate (MTX) 1.5 g/m2 infused over day 1 with leucovorin rescue, vincristine (VCR) 2 mg day 1, Ara-C 1 gm/m2 days 4 and 5, VP-16 80 mg/m2 days 4 and 5, and dexamethasone 10 mg/m2 on days 1–5. Cycles 3, 5, and 7 included the same doses of MTX, VCR, and dexamethasone, with CY 200 mg/m2 IV on days 1–5 and doxorubicin 25 mg/m2 days 4 and 5. Cycles were delivered every 21 days if blood counts had recovered. Filgrastim was given at 5μg/kg/day SC beginning day 7 of each cycle and continuing until the absolute neutrophil count recovered to > 5000/μL. Rituximab was initiated during cycle 2 on day 8 at 50 mg/m2 and on days 10 and 12 at 375 mg/m2. During cycles 3 through 7, rituximab was infused only on day 8 of each course at 375 mg/m2. Central nervous system (CNS) prophylaxis consisted of triple intrathecal therapy on day 1 of cycles 2–7 (6 total doses). Results: 27% of patients were ≥60 years old; 70% were male; 46% had intermediate or high risk disease by the IPI (Table). Overall, 75 of 105 subjects completed all 7 planned courses of therapy. 82% attained a complete response (CR), and 87% of these remain in CR at last follow up. 7% had a partial response. With median follow up of survivors of 3.2 years, 2 year event free survival (EFS) and overall survival (OS) were 77% and 79%, respectively, with a trend favoring those <60 years old (87% and 87%, respectively). There were clear differences in outcome based on IPI score with 2 year EFS and OS for low risk patients of 90% and 92% versus 55% and 55% for high risk patients, respectively (Figure). This protocol did not use prophylactic CNS radiation, and 4 pts had documented CNS relapses; 2 had intermediate and 1 high IPI disease; the 4th was unknown. Relapse after 2 years was rare. 7 subjects (6.8%) died from treatment related causes (1 CNS bleed, 4 infections, 2 respiratory failure). Nearly all subjects experienced the anticipated severe hematologic toxicities. The most common grade 3 and 4 non-hematologic toxicities included stomatitis/upper GI toxicity (∼ 66%), nausea/vomiting (20%), fatigue (26%), rash or erythema multiforme (10%), diarrhea (10%), pulmonary or CNS bleeding (11%), clinically documented infections (72%), neurologic disturbances (8%), and dyspnea (10%). 8 pts (8%) had tumor lysis syndrome (all grade 3). Conclusion: This regimen provides a high rate of durable remissions in adult patients with a manageable side effect profile. Chemoimmunotherapy should be the standard for adult patients with Burkitt leukemia/lymphoma. Disclosures: Off Label Use: Rituximab for use in Burkitt's. Cheson:Genentech: Consultancy.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17124-17124
Author(s):  
C. Amaral ◽  
I. Small ◽  
D. B. Olmedo ◽  
A. Sousa ◽  
E. Toscano ◽  
...  

17124 Background: The established treatment for T3 Pancoast tumors, radiation plus surgery, leads to a 50% R0 resection rate and a 30% 5 year survivals. T4 tumors are usually unresectable and incurable. Our group retrospectively analyzed the feasibility and efficacy of induction chemoradiotherapy plus surgery for T3 and T4 tumors. Methods: Eligible patients (pts) had biopsy proven, untreated, T3–4N0–1 Pancoast tumors. Induction therapy was cisplatin (50 mg/m2, days 1,8,29,36) and etoposide (50 mg/m2, days 1–5, 29–33) (PE) given concurrently with radiation (45 Gy, 25 daily fractions). Thoracotomy was done within 5 weeks of induction therapy for stable or responding disease. All pts were to receive postoperative chemotherapy (PE ×2). Median follow up was 19 months. Results: From 4/01–6/05, 13 eligible pts were enrolled: 6 men, 7 women, median age 53 years; 9 T3, 4 T4. All pts (100%) completed induction therapy. Grade 3–4 toxicities were neutropenia (n = 2), anemia (n = 1), fatigue (n = 1), esophagitis (n = 5). All pts had thoracotomy, 13 had R0 resection. Pathologic CR was found in 3 (23.1%), minimal microscopic disease in 1 (7.7%). Postoperative chemotherapy completed by only 1/13 pts. Median survival was not reached and Median Disease free (DFS) and 2 year overall survivals (OS) were 26 months (CI 95% 13.6–38.4) 67% for all pts, respectively. Relapse sites were brain only (n = 3) and local only (n = 1). Conclusion: This combined modality therapy was well tolerated and leads to high rates of complete resection, OS and local control that are strikingly better than with radiation and surgery. These results obtained in a population with T3 and T4 tumors reproduced those of the SWOG study in terms of resectability, safety and short-term survival Of note is the poor adherence to postoperative chemotherapy in this population. No significant financial relationships to disclose.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11102-11102
Author(s):  
G. Atalay Basaran ◽  
D. Cabuk ◽  
F. Dane ◽  
M. Teomete ◽  
S. Iyikesici ◽  
...  

11102 Background: Breast cancer patients (pts) with NN disease have diverse clinical outcomes. An optimal treatment decision- making tool has not been defined for this heterogeneous group. Methods: We identified pts with NN disease who have been treated between 1998–2006 in our department. We recorded the clinical/pathological, treatment characteristics and analyzed their survival outcome. High risk (HR) was defined as having at least one of the following features: age<35 yr-old, pts with grade 3 tumors (tms), ER and PR negative tms, tm size >2 cm. Results: Out of 597 early BC pts, 275 pts with NN disease were identified, 190 pts with HR, 85 with low risk (LR) features.The median age was 51 (26–83). The median follow up was 40 months (4–120 months). 47% pts were premenopausal. 31% pts had breast conserving surgery (BCS).58/29% pts had grade 2/3 tms. 34% pts with BCS or T3 tms received adjuvant radiotherapy. All receptor positive pts received adjuvant endocrine therapy (ET). In the HRNN group, 5% pts had tms>5cm, 51/40% pts had grade 2/3 tms, 43% pts had ER/PR negative tms. In the LRNN group 25/74% pts had grade 1/2 tms, no pt had receptor negative tm. 86%/51% pts received adjuvant chemotherapy (CT) in the HR and LRNN groups. 12%/48% pts received adjuvant ET alone in the HR and LRNN groups. 5pt in the HR and 1 pt in the LR group received no adjuvant systemic therapy due to their comorbidities and/or negative receptor status. So far, 14 pts had relapsed (8 from the HR, 6 from the LR group) and 3 pts died due to BC (1 from the HR, 2 from LR group). The 5-yr DFS was %94 in the HR and was %90 in the LR groups. HRNN pts had %98 and LRNN pts had %95 5-yr OS. Conclusion: It seems that prognostic information based merely on clinical/pathological characteristics might not accurately quantify the risk of recurrence and death, so that the decisions about adjuvant chemotherapy in NN breast cancer patients. Prospective evaluation of the performance of the new genomic prognostic tools compared to traditional prognostic factors is needed in order to more clearly define the HR vs LR subsets of NNBC pts. No significant financial relationships to disclose.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2053-2053
Author(s):  
D. A. Bota ◽  
A. Desjardins ◽  
J. A. Quinn ◽  
J. N. Rich ◽  
J. J. Vredenburgh ◽  
...  

2053 Background: We evaluated the combination of imatinib mesylate and hydroxyurea in recurrent/progressive low-grade gliomas (LGG) following the encouraging response of this combination demonstrated among adults with recurrent malignant glioma. Methods: Key eligibility criteria: age over 18 yrs; histologically confirmed grade II LGG that is recurrent/progressive following at least prior surgical resection; Karnofsky = 60% and adequate organ function. Imatinib plus hydroxyurea were given on a continuous oral daily schedule for 28 day cycles; imatinib was administered at 400 mg daily to patients not on CYP3A-enzyme inducing antiepileptic drugs (EIAED) while those on EIAED received 500 mg twice a day. All patients received 500 mg twice a day of hydroxyurea. Patients were evaluated every other month with physical and MRI examinations. Results: Twenty-seven patients with recurrent or progressive LGG have enrolled including 17 with astrocytoma and 10 with oligodendroglioma. Eleven (40.7%) are on EIAED. Median age was 42 years (range 24–66 years). 26% of patients had received prior therapy other than surgery (XRT, n=2; chemotherapy, n=5). The most frequent toxicities possibly related to the study regimen were fatigue (grade 2, n=5; grade 3, n=1), neutropenia (grade 2, n=1; grade 3, n=2), anemia (grade 2, n=2), rash (grade 2, n=2), nausea (grade 3, n=1), anorexia (grade 2, n=1), and AST elevation (grade 2, n=1). There were no grade 4 or 5 treatment-related toxicities. Among patients evaluable for response, 17 (85%) achieved stable disease and 3 (15%) had progression. Twenty patients continue on study having received 2–16 months of therapy. Additional accrual and follow-up is ongoing. Conclusions: Continuous daily treatment of imatinib plus hydroxyurea is well tolerated and associated with encouraging preliminary activity among adults with recurrent/progressive LGG. [Table: see text]


2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 91-91
Author(s):  
Maxwell Mulcahy ◽  
Linda S. House ◽  
Nicholas James Power ◽  
Julie Olson ◽  
Shauna McManus ◽  
...  

91 Background: Immunotherapy & Me ( IO & Me) is an innovative program of supportive resources developed by Cancer Support Community to investigate and support the unique needs of immunotherapy patients. Here, we describe psychosocial distress and confidence accessing resources among a sample of program participants. Methods: IO & Me is recruiting at 4 community clinics and 1 academic center. Eligible patients must be on an anti-cancer immunotherapy. At enrollment, participants consent, provide demographic/clinical history, and report level of confidence accessing cancer treatment information and resources related to treatment decision making (TDM) and managing symptoms/side effects (SEs). Distress is reported with CancerSupportSource (CSS), a tool where patients rate level of concern on 15 items. Once enrolled, participants can access educational resources (print materials, SE tracker, eLearning courses) and a toll-free helpline staffed by licensed mental health professionals (Cancer Support Helpline). Follow-up surveys are available every 30 days for 6 months. We present data from 68 participants at enrollment and 22 at first follow-up. Results: Participants were 87% White; 69% male; mean age = 65 years (SD = 13). 43% had lung cancer; 22% melanoma; 9% kidney cancer. At baseline, the frequency who felt very or extremely confident accessing resources related to: TDM = 68%; managing SEs = 60%; treatment information = 75%. For distress, top concerns were: fatigue (35% of participants); health insurance/money worries (34%); exercise/physical activity (32%). After 30 days, the frequency who felt confident accessing resources for: TDM = 100%; managing SEs = 91%; treatment information = 100%. Top concerns were: changes/disruptions in work, school, or home life (14%); feeling irritable (9%); sleep problems (9%). Conclusions: Preliminary results show greater variability in distress and confidence accessing resources at baseline than 1-month into the program, at which time few endorse cancer-related concerns and most feel confident accessing resources. These findings highlight the utility of providing patients with educational/support resources and the value of customizable programs like IO & Me. Clinical trial information: NCT03347058.


1995 ◽  
Vol 83 (4) ◽  
pp. 583-589 ◽  
Author(s):  
Leslie N. Sutton ◽  
Patricia T. Molloy ◽  
Heidi Sernyak ◽  
Joel Goldwein ◽  
Peter L. Phillips ◽  
...  

✓ The feasibility of radical surgery for astrocytomas of the optic chiasm/hypothalamus has been reported by several groups. Such surgery carries significant risks, however, including permanent damage to the pituitary gland, optic apparatus, hypothalamic structures, and carotid arteries. The benefits of radical surgery, both in terms of efficacy and toxicity, should, therefore, be evaluated against standard therapy, as is usually done for new chemotherapeutic protocols. To this end, a retrospective review was performed of 33 patients treated at Children's Hospital of Philadelphia between 1976 and 1991 who met criteria that would have made them eligible for radical surgery in many centers today, but were treated with either no surgery or conservative surgery (< 50% resection) or biopsy followed by adjuvant therapy with local radiation therapy (29 patients) and/or chemotherapy with actinomycin-D and vincristine (18 patients). The review encompassed all children with a globular enhancing mass of at least 2 cm in the hypothalamic/chiasmatic region, no evidence of optic nerve involvement or involvement of the optic radiations by computerized tomography or magnetic resonance imaging, and follow up of at least 3 years. All but one patient had tissue confirmation of a low-grade or pilocytic astrocytoma. Thirteen of the patients were 2 years of age or younger at diagnosis. Five individuals died: three of tumor progression, one of acute shunt malfunction, and one of intercurrent infection. The remaining 28 were alive at last follow up, a mean of 10.9 years from diagnosis. Twenty-three surviving patients have functional vision in at least one eye, 12 require no endocrine replacement, and 16 are in or have completed schooling with regular academic requirements. If radical surgery is to become standard care for children with low-grade astrocytomas of the hypothalamic/chiasmatic region, long-term survival and functional outcome will have to equal or surpass those of historical controls who were treated conservatively.


Sign in / Sign up

Export Citation Format

Share Document