A randomised phase II trial of 1month versus 1year of adjuvant high-dose interferon α-2b in high-risk acral melanoma patients

e21516 Background: The clinical efficacy of PD-1 inhibitors as an adjuvant treatment for Asian melanoma patients has not yet been determined. Methods: Thus, this single-centre, retrospective study analysed the clinical data of 90 Chinese patients with completely resected, stage III cutaneous or acral melanoma who received either adjuvant PD-1 inhibitor or high-dose interferon α-2b (HDI). Propensity score matching (PSM) was used to control baseline differences between the two treatment groups. The primary end point was recurrence-free survival (RFS), and the secondary end points included distance metastasis-free survival (DMFS) and incidence of first distant metastatic sites. Results: Anti-PD-1 treatment resulted in significantly longer RFS (18-month RFS, 53.3% versus 26.7%; 95% CI, 0.097-0.975; P < 0.05) and DMFS (18-month DMFS, 70.9% versus 46.1%; 95% CI, 0.13-0.945; P < 0.05) than HDI in cutaneous melanoma patients. However, adjuvant anti-PD-1 treatment had no advantage over HDI in acral melanoma patients (18-month RFS, 30.0% versus 35.9%; P > 0.05; 18-month DMFS, 36.5% versus 63.6%; P > 0.05). The incidence of lung metastasis at first in the anti-PD-1 group was found to be significantly lower (12.5% versus 48.5%; P < 0.05) in cutaneous melanoma patients than in acral melanoma patients, but no difference in metastatic sites were observed between the two treatment groups among acral melanoma patients. The incidence of treatment-related AEs was similar between the two treatment groups. Conclusions: In conclusion, adjuvant anti-PD-1 treatment was well tolerated and yielded a significantly better prognosis than HDI in Chinese patients with stage IIIB/C cutaneous melanoma, but a significant difference was not observed in those with acral melanoma.

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Systemic Immune-Inflammation Index and Circulating T-Cell Immune Index Predict Outcomes in High-Risk Acral Melanoma Patients Treated with High-Dose Interferon

Translational Oncology ◽

10.1016/j.tranon.2017.06.004 ◽

2017 ◽

Vol 10 (5) ◽

pp. 719-725 ◽

Cited By ~ 9

Author(s):

Jiayi Yu ◽

Xiaowen Wu ◽

Huan Yu ◽

Siming Li ◽

LiLi Mao ◽

...

Keyword(s):

T Cell ◽

High Risk ◽

High Dose ◽

Acral Melanoma ◽

Melanoma Patients ◽

Immune Inflammation ◽

High Dose Interferon

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Association of immune-inflammation index with outcome of high-risk acral melanoma patients treated with adjuvant high-dose interferon.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.15_suppl.e21070 ◽

2016 ◽

Vol 34 (15_suppl) ◽

pp. e21070-e21070 ◽

Cited By ~ 3

Author(s):

Jiayi Yu ◽

Si Ming Li ◽

Yan Kong ◽

Lu Si ◽

Xinan Sheng ◽

...

Keyword(s):

High Risk ◽

High Dose ◽

Acral Melanoma ◽

Melanoma Patients ◽

Immune Inflammation ◽

High Dose Interferon

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Lymphocyte Subpopulations and Interleukin Levels in High-Risk Melanoma Patients Treated With High-Dose Interferon A-2B

American Journal of Clinical Oncology ◽

10.1097/00000421-200212000-00013 ◽

2002 ◽

Vol 25 (6) ◽

pp. 591-596 ◽

Cited By ~ 4

Author(s):

Helen Gogas ◽

George Paterakis ◽

Konstantina Frangia ◽

Dimitrios Bafaloukos ◽

Dimitrios Pectasides ◽

...

Keyword(s):

High Risk ◽

Lymphocyte Subpopulations ◽

High Dose ◽

High Risk Melanoma ◽

Risk Melanoma ◽

Melanoma Patients ◽

High Dose Interferon

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High-Dose Interferon Alfa-2b Does Not Diminish Antibody Response to GM2 Vaccination in Patients With Resected Melanoma: Results of the Multicenter Eastern Cooperative Oncology Group Phase II Trial E2696

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.5.1430 ◽

2001 ◽

Vol 19 (5) ◽

pp. 1430-1436 ◽

Cited By ~ 103

Author(s):

John M. Kirkwood ◽

Joseph Ibrahim ◽

David H. Lawson ◽

Michael B. Atkins ◽

Sanjiv S. Agarwala ◽

...

Keyword(s):

High Risk ◽

Phase Ii ◽

Interferon Alfa ◽

Immunoglobulin M ◽

Phase Iii ◽

High Dose ◽

High Risk Melanoma ◽

Risk Melanoma ◽

High Dose Interferon ◽

Very High

PURPOSE: High-dose interferon alfa-2b (IFNα2b) is the only established adjuvant therapy of resectable high-risk melanoma. GM2-KLH/QS-21 (GMK) is a chemically defined vaccine that is one of the best developed of a range of vaccine candidates for melanoma. A single-institution phase III trial conducted at Memorial Hospital served as the impetus for an intergroup adjuvant E1694/S9512/C509801 trial, which recently completed enrollment of 880 patients. To build on the apparent benefit of IFNα2b in resectable high-risk American Joint Committee on Cancer (AJCC) stage IIB or III melanoma, this phase II study was designed to evaluate the combination of GMK and IFNα2b. The E2696 trial was undertaken to evaluate the toxicity and other effects of the established adjuvant high-dose IFNα2b regimen in relation to immune responses to GMK and to evaluate the potential clinical and immunologic effects of the combined therapies. PATIENTS AND METHODS: This trial enrolled 107 patients with resectable high- or very high–risk melanoma (AJCC stages IIB, III, and IV). RESULTS: The results demonstrate that IFNα2b does not significantly inhibit immunoglobulin M or G serologic responses to the vaccine and that the combination of high-dose IFNα2b and GMK is well tolerated in this patient population. CONCLUSION: Cox analysis of the results of the combination with IFNα2b show improvement in the relapse-free survival of patients with very high–risk melanoma (including those with resectable M1 disease).

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Imatinib 800 mg: Preliminary Results of a Phase II Trial of the GIMEMA CML Working Party in Intermediate Sokal Risk Patients and Status-of-the-Art of an Ongoing Multinational, Prospective Randomized Trial of Imatinib Standard Dose (400 mg Daily) vs High Dose (800 mg Daily) in High Sokal Risk Patients.

Blood ◽

10.1182/blood.v106.11.1098.1098 ◽

2005 ◽

Vol 106 (11) ◽

pp. 1098-1098

Author(s):

Gianantonio Rosti ◽

Giovanni Martinelli ◽

Fausto Castagnetti ◽

Nicoletta Testoni ◽

Giorgina Specchia ◽

...

Keyword(s):

High Risk ◽

Randomized Trial ◽

Phase Ii ◽

Response Rate ◽

Phase Ii Trial ◽

Standard Dose ◽

Phase Iii ◽

High Dose ◽

Molecular Response ◽

Risk Patients

Abstract The conventional treatment of chronic myeloid leukemia (CML) in early chronic phase (ECP) is imatinib 400 mg daily. The estimated rates of major (MCgR) and complete cytogenetic response (CCgR) at 42 months are 91% and 84%, respectively (IRIS Trial - F Guilhot, ASH 2004), with a survival free from accelerated and blastic phase of 84%. The rates of CCgR are significantly different according to Sokal score, being 91%, 84% and 69% for low, intermediate and high risk categories. Phase I and II trials of imatinib have clearly shown a dose-response effect; more importantly, a single center phase II trial of imatinib 800 mg in ECP showed significantly better results vs standard dose, in terms of CCgR (90% vs 74%) and of complete molecular response (28% vs 7% at 18 months) [H. Kantarjian et al, Blood 103 (8), 2004]. The GIMEMA (Gruppo Italiano Malattie Ematologiche dell’Adulto) CML WP is conducting a phase II trial of imatinib 800 mg in intermediate Sokal risk in ECP (trial CML/021). Overall, 89 pts (mean age 53 yrs) have been enrolled. Fourty-four patients completed 6 months of treatment: the complete hematological response rate is 100%; the MCgR and CCgR are 90% and 81%, respectively. The 6 months CCgR rate of this trial parallels the IRIS trial one in intermediate risk cases (84%), with a much shorter treatment period. The major molecular response rate at 6 months (RTQ-PCR as ratio BCR-ABL/ABL) is 56% (cut-off ≤ 0.12%) or 41% (cut-off ≤0.05%). The compliance to the treatment improved time by time, being 47% the patients receiving ≥ 80% of the scheduled dose between months 1–3 and 60% between months 4 - 6. A second project, exploring imatinib high dose, is reserved to high risk cases: a multinational working group, within the frame of Leukemianet CML WP, is conducting a phase III randomized trial (1:1) of imatinib 400 mg vs 800 mg in high Sokal risk in ECP. By July 31, 2005, 80 patients have been enrolled: GIMEMA CML WP (44 pts), Nordic Countries - Sweden, Denmark, Norway and Finland (25 pts), Turkey (10 pts) and Israel (1 pt).

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Prolonged Survival with Low Incidence of CNS Relapse and Late Toxicities in a Retrospective Series of 278 Young Patients with High-Risk (aa-IPI 2–3) Diffuse Large B-Cell Lymphoma Treated with Intensified Chemotherapy with or without Rituximab At Diagnosis

Blood ◽

10.1182/blood.v118.21.1606.1606 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1606-1606

Author(s):

Annalisa Chiappella ◽

Alessia Castellino ◽

Maria Giuseppina Cabras ◽

Anna Marina Liberati ◽

Andrea Evangelista ◽

...

Keyword(s):

High Risk ◽

Phase Ii ◽

Phase Ii Trial ◽

B Cell Lymphoma ◽

High Dose ◽

Secondary Malignancies ◽

Large B Cell Lymphoma ◽

Cns Relapse ◽

Dose Dense

Abstract Abstract 1606 Introduction. Diffuse Large B-cell Lymphoma (DLBCL) patients at high-risk (age-adjusted International Prognostic Index (aa-IPI) 2–3), had a dismal prognosis if treated with conventional chemotherapy. The introduction of intensive regimens and the addition of monoclonal antibody anti-CD20, improved prognosis, but some issues remain unresolved such as: the risk of central nervous system (CNS) relapses and the incidence of late toxicities. We analyzed a series of young DLBCL patients at high-risk consecutively treated in four prospective trials by the Italian Lymphoma Foundation (FIL) with the aim to assess the risk of CNS relapses and late toxicities in this series of patients with a prolonged follow-up Methods. From 1986 to 2006, 278 patients with DLBCL with aa-IPI 2–3 at diagnosis, were enrolled in four consecutive trials previously reported. Thirty-two into a phase II study, treated with 12 weekly infusion of MACOP-B; 39 into a phase II trial with eight weekly MACOP-B infusions followed by high-dose cytarabine, mitoxantrone and dexamethasone (MAD) plus standard BEAM and autologous stem cell transplantation (ASCT); 95 in a phase III trial that randomized high-dose sequential (HDS) chemotherapy plus ASCT (45 patients) vs six courses of dose-dense intensified CHOP (iCHOP) (50 patients); 112 into a phase II trial with four courses of iCHOP in combination with Rituximab followed by Rituximab-MAD + BEAM and ASCT. CNS prophylaxis was not mandatory in the four protocols. Updated data regarding of survival, CNS relapses and late toxicities were recorded on June 2011. Results. Clinical characteristics were: aa-IPI 2 in 55%, aa-IPI 3 in 45%, PS > 2 in 66%, LDH upper normal value in 89%, number of extranodal sites > 2 in 35%, bone marrow involvement in 27% of patients, with no statistical differences between the four trials. With a median follow-up of five years, 5-year Overall Survival (OS) was 63% (95% CI: 57–69%) in the whole series; 5-year OS by treatment was 41% (95%CI: 24–74%) in MACOPB, 54% (95%CI: 37–68%) in MACOPB+MAD+BEAM and ASCT; 53% (95%CI: 38–67%) in HDS+ASCT; 58% (95%CI: 43–70%) in iCHOP; 79% (95%CI: 70–86%) in R-iCHOP+R-MAD+BEAM and ASCT. In a multivariate analysis, the risk of death was significantly reduced in R-iCHOP+R-MAD+BEAM and ASCT (p<.001) and was adversely influenced by age with a progressive increase of five years at diagnosis (p.008) or aa-IPI3 (p.001). Four patients experienced CNS relapses, three of them in R-iCHOP+R-MAD+BEAM and ASCT and one in MACOPB. Only one of the four patients received CNS prophylaxis with intrathecal Methotrexate, even if all of them were at risk for CNS relapse according to Italian Society of Hematology guidelines (Barosi, Hematol 2006). Cumulative incidence of CNS recurrence at 10 years for R-iCHOP+R-MAD+BEAM and ASCT regimen was 3.6% (0 to 7.8). Most frequent late toxicities were dyslipidemia and secondary amenorrhea. Regarding to secondary malignancies, myelodisplasia or acute myeloid leukemia were recorded in three patients, two of them treated with R-iCHOP+R-MAD+BEAM and ASCT, at a median time of seven years off therapy. The actuarial risk of secondary malignancies at 10 years for R-iCHOP+R-MAD+BEAM and ASCT was 4.2% (0 to 10). Conclusions. The addition of Rituximab to dose-dense iCHOP plus high-dose chemotherapy plus BEAM and ASCT improved the outcome in young untreated DLBCL patients at poor prognosis, with an acceptable risk of secondary malignancies and late toxicities. A careful identification of patients at risk could avoid the risk of CNS relapse. Disclosures: Vitolo: Roche Italy: Speakers Bureau; Celgene: Speakers Bureau; Jannsen-Cilag: Speakers Bureau.

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