Adjuvant Therapy For High-risk Melanoma Research Articles

Adjuvant Therapy for High-Risk Melanoma: An In-Depth Examination of the State of the Field.

The consideration of systemic adjuvant therapy is recommended for patients with stage IIB-IV melanoma who have undergone surgical resection due to a heightened risk of experiencing melanoma relapse and mortality from melanoma. Adjuvant therapy options tested over the past three decades include high-dose interferon-α, immune checkpoint inhibitors (pembrolizumab, nivolumab), targeted therapy (dabrafenib-trametinib for BRAF mutant melanoma), radiotherapy and chemotherapy. Most of these therapies have been demonstrated to enhance relapse-free survival (RFS) but with limited to no impact on overall survival (OS), as reported in randomized trials. In contemporary clinical practice, the adjuvant treatment approach for surgically resected stage III-IV melanoma has undergone a notable shift towards the utilization of nivolumab, pembrolizumab, and BRAF-MEK inhibitors, such as dabrafenib plus trametinib (specifically for BRAF mutant melanoma) due to the significant enhancements in RFS observed with these treatments. Pembrolizumab has obtained regulatory approval in the United States to treat resected stage IIB-IIC melanoma, while nivolumab is currently under review for the same indication. This review comprehensively analyzes completed phase III adjuvant therapy trials in adjuvant therapy. Additionally, it provides a summary of ongoing trials and an overview of the main challenges and future directions with adjuvant therapy.

MRNA Vaccine Slows Melanoma Recurrence.

Findings from the phase IIb KEYNOTE-942 trial indicate that the investigational vaccine mRNA-4157/V940 plus pembrolizumab is a potential adjuvant therapy for high-risk melanoma. Following surgery, patients who received the combination experienced a significant reduction in disease recurrence risk, compared with those given just PD-1 inhibitor.

1069P Granulomatous and sarcoid-like immune adverse events following CTLA4 and PD1 blockade adjuvant therapy of high-risk melanoma: A combined analysis of ECOG-ACRIN E1609 and SWOG S1404 phase III trials

Treatment with immune checkpoint inhibitors (ICIs) has been linked to granulomatous and sarcoid-like lesions (GSL) affecting the skin, lungs, thoracic lymph nodes, eyes and other organs. Accurate diagnosis and reporting of such rare events are essential to clinical practice and patient care.

United States Intergroup E1609: A phase III randomized study of adjuvant ipilimumab (3 or 10 mg/kg) versus high-dose interferon-α2b for resected high-risk melanoma.

9504 Background: Phase III adjuvant trials reported significant benefits in relapse-free survival (RFS) for 6 FDA-approved regimens and overall survival (OS) for HDI and ipi10 versus observation or placebo. E1609 evaluated the relative safety and efficacy of ipi at 3 and 10 mg/kg compared to HDI, which was the adjuvant standard until recently. Methods: E1609 had 2 co-primary endpoints: OS and RFS; considered positive if either co-primary endpoint comparison was positive. Activated on 5/25/2011 and completed accrual 8/15/2014. A 2-step hierarchical approach evaluated ipi3 vs HDI followed by ipi10 vs HDI. Patients were stratified by AJCC7 stage (IIIB, IIIC, M1a, M1b). Based on protocol criteria, the primary evaluation was conducted using a data cutoff of 2/15/2019. Results: Final adult patient accrual was 1670; 523 randomized to ipi3, 636 to HDI and 511 to ipi10. Treatment related adverse events (AEs) Grade 3 or higher were experienced by 37% pts with ipi3, 79% with HDI and 58% with ipi10, and those of any grade leading to treatment discontinuation were 35% with ipi3, 20% HDI and 54% ipi10. AEs were mostly immune related and consistent with the known toxicity profiles of these agents. Gr5 AEs considered at least possibly related were 3 with ipi3, 2 with HDI and 8 with ipi10. First step comparison of OS and RFS of ipi3 vs. HDI utilized an ITT analysis of concurrently randomized cases (N = 1051) and showed significant OS difference in favor of ipi3; HR 0.78, 95.6% RCI (.61, 1.00); p = 0.044. The prespecified efficacy boundary was crossed. For RFS, HR 0.85, 99.4% CI (.66, 1.09), p = 0.065. In the 2nd step comparison of ipi10 vs. HDI (N = 989), there were trends towards improvement in OS [HR 0.88, 95.6% CI (.69, 1.12)] and RFS [HR 0.84, 99.4% CI (.65, 1.09)] in favor of ipi10 that were not statistically significant. Conclusions: Adjuvant therapy with ipi3 benefits survival of resected high-risk melanoma pts; for the first time in the history of melanoma adjuvant therapy, E1609 has demonstrated a significant improvement in the primary endpoint of OS against an active control regimen previously shown to have OS and RFS benefits, supporting early systemic adjuvant therapy for high-risk melanoma. Clinical trial information: NCT01274338.

A pilot study of interferon-alpha-2b dose reduction in the adjuvant therapy of high-risk melanoma

Melanoma is a highly immunogenic tumor and consequently, efforts have been centered on the development of immune-based treatments for this malignancy [1]. Interferons were initially described in the mid-1950s as proteins that interfere with viral replication [2, 3]. Interferons are cytokines that activate Janus kinases (Jak), which lead to phosphorylation and activation of transcription factors belonging to the signal transducer and activator of transcription (STAT) family [4, 5]. Interferon-alpha (IFN-α) became available for use in clinical trials in the mid-1980s [6]. Results suggested that IFN-α inhibited the proliferation of malignant cells and stimulated immune effectors; therefore, IFN-α was initially used in patients with advanced disease [7, 8]. Since then, several meta-analyses have demonstrated that high-dose adjuvant IFN-α (daily 20 MU/m2 intravenous induction therapy for 1 month followed by maintenance subcutaneous 10 MU/m2 three times per week for at least 1 year) can prolong the disease-free interval in high-risk melanoma patients [9]. The introduction of checkpoint inhibitor therapy has revolutionized the adjuvant therapy of melanoma; however, there remains a role for IFN-α in this setting based on the potential for cancer immune escape or autoimmune events with CTLA-4 and PD-1 blocking antibodies [10–14]. There has also been significant advances in mitogen-activated protein kinase (MAPK) targeted therapies, particularly for BRAF (an intracellular signaling kinase) and MEK (signaling molecule downstream of BRAF). A recent clinical trial demonstrated significant improvement in both relapse-free survival and overall survival with adjuvant dabrafenib (BRAF inhibitor) plus trametinib (MEK inhibitor) in patients with stage III melanoma. These therapies are now approved for adjuvant therapy in BRAF mutated tumors [15]. However, since only approximately 40–50% of melanoma cells harbor an activating BRAF mutation, there still remains a role for IFN-α in this setting as the remaining 50–60% of melanomas would not be susceptible to BRAF-targeted therapies. IFN-α activates the Jak-STAT signaling pathway and induces synthesis of hundreds of different proteins [4, 5]. Our group has shown that STAT1-mediated gene regulation within immune effectors is necessary for mediating the anti-tumor effects of IFN-α and also that the amount IFN-α administered to melanoma patients is likely in excess of the optimal biological dose [4]. Indeed, high doses of IFN-α appear to be no more effective in the induction of phosphorylated STAT1 (p-STAT1) and in the transcription of interferon-stimulated genes (ISGs) than intermediate doses [16, 17]. Our group’s studies in genetically manipulated mice have shown that suppressors of cytokine signaling-1 (SOCS1) and SOCS3 negatively regulate IFN-induced Jak-STAT signal transduction, gene regulation and anti-melanoma activity, and that high doses of IFN-α can induce SOCS proteins [18, 19]. We hypothesized that lower doses of IFN-α would be superior for induction of IFN signal transduction in patient immune cells. A prospective clinical trial was performed wherein patients eligible for adjuvant IFN-α-2b received 1 month of standard intravenous high-dose IFN-α-2b (20 MU/m2) followed by subcutaneous IFN-α-2b at a dose of 10 MU/m2 with dose reductions at set intervals down to a level of 4 MU/m2. Jak-STAT signal transduction and transcription of ISGs in patient peripheral blood mononuclear cells (PBMCs) were monitored during the course of adjuvant IFN-α therapy. The objective of this pilot study was to determine if lower doses of IFN-α were as effective in the induction of IFN signal transduction and gene expression as the standard high dose regimen.

5-(3,3-Dimethyle-1-Triazeno) Imidazole-4-Carboxamide and Interleukin-2 Adjuvant Therapy in Resected High-Risk Primary and Regionally Metastatic Melanoma

BackgroundIn the precheckpoint inhibitor era, high-dose interferon was the only approved adjuvant therapy for high-risk melanoma. In this manuscript, we analyze the recurrence-free survival, overall survival and toxicity profile of adjuvant treatment with interleukin-2 (IL-2) and 5-(3,3-dimethyle-1-triazeno) imidazole-4-carboxamide (DTIC) for resected high-risk melanoma patients. MethodsAll patients with stage IIB, IIC or stage III melanoma who were treated with DTIC/IL-2 combination therapy at a single institution from 2000 to 2010 were identified from the University of Louisville Hospital medical record. Patients received 6 months of subcutaneous IL-2 (12 × 106 units days 1-4) and intravenous DTIC (750 mg/m2 day 1 of each cycle) every 28 days for 6 cycles. Individual medical records were accessed to collect the data. ResultsOf the 112 patients treated, all underwent surgical resection and then received adjuvant treatment. A total of 58.7% of the patients were male, 42.2% female; 99% were Caucasian. A total of 79 (72.5%) of the patients were alive at the time of analysis and 57 (47.7%) patients were currently event free. A total of 69 (63.3%) patients completed all 6 months of adjuvant combination treatment with 13.8% of the patients requiring IL-2 and 21.1% of the patients requiring DTIC dose reduction. Five year overall survival was 75.57% with recurrence-free survival of 53.05%. ConclusionsFor several decades, there has not been an ideal adjuvant treatment for patients with resected high risk melanoma. Our retrospective analysis suggests that combination therapy with DTIC/IL-2 is beneficial and relatively well tolerated as an alternative adjuvant treatment for patients with high-risk melanoma.

A phase III randomized study of adjuvant ipilimumab (3 or 10 mg/kg) versus high-dose interferon alfa-2b for resected high-risk melanoma (U.S. Intergroup E1609): Preliminary safety and efficacy of the ipilimumab arms.

9500 Background: In the U.S., 3 regimens have regulatory approval as adjuvant therapy for high-risk melanoma, including high-dose interferon-alfa (HDI) and ipilimumab 10 mg/kg (ipi10). Ipilimumab 3 mg/kg (ipi3) has regulatory approval for metastatic inoperable melanoma. The toxicity of ipi is dose- dependent, and following the recent approval of adjuvant ipi10, it has become urgent to evaluate the relative safety and efficacy of adjuvant ipi at the 2 dose levels that have been tested in E1609. Methods: E1609 randomized patients (pts) with resected high-risk melanoma (stratified by stages IIIB, IIIC, M1a, M1b) to ipi10 or ipi3 versus HDI. Co-primary endpoints were RFS and OS. The current analysis investigates the relative safety and preliminary, non-comparative RFS of the ipi arms as of 3/2/17. Results: E1609 was activated on 5/25/11 and completed adult pt accrual on 8/15/14. Accrual to ipi10 was suspended due to toxicity between 9/23-11/16/2013. Final adult pt accrual was 1670 including 511 ipi10, 636 HDI and 523 ipi3 pts. Treatment related adverse events (AEs) were reported among 503 ipi10 and 516 ipi3 pts. Worst degree (Gr 3+) AEs were experienced by 57% ipi10 and 36.4% ipi3 pts and were mostly immune related (Table 1). AEs led to discontinuation of treatment in 271 (53.8 %) of 503 ipi10 and in 180 (35.2 %) of 512 ipi3 pts during the initial 4 dose induction phase. Gr5 AEs considered at least possibly related were 8 with ipi10 and 2 with ipi3. At a median follow-up of 3.1 years, an unplanned RFS analysis of ipi3 and ipi10 on concurrently randomized pts showed no difference between the 2 arms. Three-year RFS rate was 54% (95% CI: 49, 60) with ipi10 and 56% (50, 61) with ipi3. Conclusions: Adjuvant therapy of pts with high-risk melanoma is associated with significantly more toxicity at ipi10 compared to ipi3. An unplanned RFS analysis of concurrently randomized pts on the 2 ipi arms showed no difference in RFS. Clinical trial information: NCT01274338. [Table: see text]

Long-Term Outcomes and Prognostic Factors of High-Risk Malignant Melanoma Patients after Surgery and Adjuvant High-Dose Interferon Treatment: A Single-Center Experience

Background: Surgical excision constitutes an important part of the treatment of local advanced malignant melanoma. Due to the high recurrence risk, adjuvant high-dose interferon therapy is still the only therapy used in stage IIB and III high-risk melanoma patients. Methods: One hundred two high-risk malignant melanoma patients who received high-dose interferon-α-2b therapy were evaluated retrospectively. The clinicopathological features, survival times, and prognostic factors of the patients were determined. Results: The median disease-free and overall survival times were 25.2 and 60.8 months, respectively. Our findings revealed that male gender, advanced disease stage, lymph node involvement, lymphatic invasion, the presence of ulceration, and a high Clark level were significant negative prognostic factors. Conclusion: In light of the favorable survival results obtained in this study, high-dose interferon treatment as adjuvant therapy for high-risk melanoma is still an efficient treatment and its possible side effects can be prevented by taking the necessary precautions.

Systemic treatment of cutaneous and mucosal melanoma.

On behalf co-editors, Drs. Antonio Buzaid, Jun Guo and Sanjiv Agarwala, it is a pleasure to welcome you to this special edition on melanoma. While not a very common disease in China, the many dramatic and recent advances in melanoma have made this a paradigm for the success of immunotherapy and targeted treatment of cancer in general. In other words, research in melanoma is creating a revolution in the understanding of tumor biology and is teaching us how to treat other cancers using a more rational approach. In this issue we bring you articles written by experts from China and around the world. Despite all the exciting advances in therapy of advanced melanoma, prevention of metastatic disease is ideal, and we start with a discussion on the current status of adjuvant therapy of high-risk melanoma. An understanding of the genotyping of melanoma is critical to addressing new therapies and this is discussed next. We follow with a detailed analysis of therapy for advanced melanoma using check point inhibitors and targeted agents and also go over management of potential toxicities while using these agents. Mucosal melanoma is unique subset of melanoma that is still a bit of a mystery to clinicians in the West due to it being rare in those populations. We are pleased to offer the most comprehensive reviews on the current status of mucosal melanoma including genotyping, adjuvant therapy, the use of targeted agents and checkpoint inhibitors and a proposed treatment algorithm for this unique subset of melanoma patients. Finally, we have put together an overall treatment algorithm for melanoma as it stands today in 2014. This is based on the authors’ best clinical judgment and experience based on the current evidence in the literature, and we are confident that this will help provide a framework for decision making in the clinic. We hope you will enjoy this issue and that it will enhance your understanding of this challenging disease.

Impact of health care professional interventions on completion of therapy in patients receiving high-dose interferon-alfa 2b adjuvant therapy for high-risk melanoma.

e20038^ Background: Melanoma incidence increased dramatically in the last decades. Intron A is the only adjuvant therapy shown to significantly increase progression-free and overall survival in hig...

Advances in Adjuvant Therapy for the Treatment of High-risk Melanoma

The global incidence of melanoma is increasing, and the prognosis for patients remains poor. High-dose interferon-alpha (HD-IFN-a) and pegylated IFN are the only US Food and Drug Administration (FDA)-approved agents for adjuvant therapy for high-risk melanoma, and an improvement in relapse-free survival (RFS) has been observed consistently across nearly all published studies and meta-analyses. Some studies and meta-analyses have also supported an overall survival (OS) benefit. However, despite a number of adjuvant studies, controversy remains regarding the role of this treatment. As the benefits in OS are modest with IFN treatment, there is therefore a need for new therapeutic targets, new drugs, and optimum patient selection. Current research is investigating new adjuvant agents, either individually or in combination, which may advance the standard of care beyond HD-IFN. Additionally, identifying biomarkers of patients with greater likelihood of response may allow patient-specific therapeutic approaches. Following the recent FDA approval of ipilimumab, vemurafenib, dabrafenib, and trametenib for metastatic melanoma, ongoing adjuvant trials are now underway.

Adjuvant interferon therapy for malignant melanoma:the debate

Based on the results of the Kirkwood high-dose interferon alpha-2b (HDI) adjuvant therapy trial of the Eastern Cooperative Oncology Group 1684, the US Food and Drug Administration (FDA) approved HDI as the postoperative adjuvant therapy for high-risk melanoma. Unfortunately, controversies continue regarding the use of interferon (IFN) as adjuvant therapy for melanoma owing to the inconsistent results of subsequent trials. Numerous trials of adjuvant interferon therapy demonstrated a benefit in terms of relapse-free survival (RFS), but without confirmed significant effect on overall survival (OS). The optimal timing, dose, and type of interferon are not yet defined. Therefore, adjuvant interferon treatment is preferentially applied in the randomized clinical trials in specialized centers. Decisions about the appropriateness of adjuvant interferon alfa-2b treatment for patients should be made on an individual basis, after discussion with the patient, including an explanation of the potential benefits and side effects of interferon therapy. Moreover, we also need to use available regimens reasonably, seek feasible and predictable prognostic factors to serve patients with individualized therapy.

Screening tools for interferon-related cognitive decline in melanoma patients.

8539 Background: Interferon α-2b (IFN) is the only approved adjuvant therapy for high-risk melanoma. IFN-related cognitive deficiencies and mood alterations have been reported. Antidepressants are able to remedy mood, but therapies targeting the cognitive effects of IFN are lacking. Development of therapies requires validation of quantitative measures of cognitive dysfunction in this population. Methods: Melanoma patients who received 1 month high-dose IFN (n = 9), were compared to IFN eligible patients (> stage IIA) who declined therapy (n = 10). Five cognitive function tests were administered: mini-mental status exam, Hopkins Verbal Learning Test-Revised (HVLT), controlled oral word association test (COWAT), Ruff 2 and 7 and Trail Making Tests A and B. The Profile of Mood States-Short Form (POMS) was used to assess mood changes. Test scores were compared as the change from baseline to after IFN or 1-3 months of observation. Welch's t test was used to determine significance. Results: Significant differences were seen in the COWAT, HVLT and POMS. COWAT results showed a significant decrease in word generation (p = 0.013) in IFN patients. HVLT results showed a significant decrease in immediate recall (p = 0.017), but no change in delayed recall or recognition. Significant self-reported mood changes included increased fatigue (p = 0.034), decreased vigor (p = 0.046) and increased confusion (p = 0.034). 8 of 9 IFN patients scored 1 standard deviation (SD) below the observation patient mean on at least one cognitive function test. 5 patients scored 1 SD below on either the HVLT or COWAT. 3 patients scored 1 SD below on the HVLT while 4 scored 1 SD below on the COWAT. Conclusions: In this pilot study, COWAT and HVLT results demonstrate neurocognitive differences between IFN-treated and untreated melanoma patients. It may be possible to use these tests to screen for cognitive dysfunction in IFN patients. Based on these preliminary results, the combination of COWAT and the HVLT immediate recall item is most sensitive. COWAT alone may be more practical than the combination, as it is freely available, easy to administer, and has a sensitivity of 80% vs. the combination. These results must be validated in a larger population and correlated with functional impairment. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Schering-Plough Merck, Schering-Plough

Clinical and Immunologic Basis of Interferon Therapy in Melanoma

Interferon alpha2b (IFN-alpha2b) at high dosage is critical to the reversal of signaling defects in T cells of melanoma patients, and to the durable effector (alpha DC1) polarization of dendritic cells. These immunoregulatory effects appear to be uniquely achieved with levels of IFN-alpha only attainable in vivo using the high-dose regimen of IFN-alpha2b (HDI). Three US cooperative group studies have evaluated the benefit of HDI as an adjuvant therapy for high-risk melanoma. All have demonstrated significant and durable reduction in the frequency of relapse, while the first and third trials have demonstrated significant improvements in the fractions of patients surviving compared with observation (E1684) or with a ganglioside vaccine (GMK, E1694). A meta-analysis of 13 randomized trials evaluating adjuvant IFN therapy has now also demonstrated significant benefits for IFN in terms of RFS and OS. Research of IFN-alpha in melanoma is now focused on identifying prognostic markers of outcome and predictors of therapeutic response.

STAT3 as a Biomarker of Progression in Atypical Nevi of Patients with Melanoma: Dose–Response Effects of Systemic IFNα Therapy

STAT3 as a Biomarker of Progression in Atypical Nevi of Patients with Melanoma: Dose–Response Effects of Systemic IFNα Therapy

INV 24 Historic overview and review of current strategies of adjuvant therapy for high-risk melanoma

INV 24 Historic overview and review of current strategies of adjuvant therapy for high-risk melanoma

Linking Interferon Response with Autoimmunity

The use of interferon alfa-2b (IFN-α2b) as adjuvant therapy for high-risk melanoma has been controversial since it was first found to have

Building Upon the Standard of Care in Adjuvant Therapy of High-Risk Melanoma

Melanoma is the fifth most frequent cancer among males and the sixth most frequent cancer in females. It takes a toll in productive life years that is exceeded only by childhood cancers and testicular carcinoma. Melanoma incidence has increased consistently during the past two generations. However, the depth of primary tumor invasion—the cardinal prognostic factor of localized primary melanoma—has decreased. As a consequence, the case fatality rate has decreased from 50% to less than 10% during the past 50 years. Despite these advances, 8,000 deaths in the United States each year are attributable to melanoma. The death rate has increased 157% in the past decade among older men, a subset of the population who present with thicker lesions ( 4.0 mm) that may have evaded detection or may represent a biologically different process. Against this background, it is daunting that no therapy has ever shown a significant prolongation of survival in large, properly conducted, randomized clinical trials for metastatic disease. Only one, interferon alfa-2b (IFN -2b), has shown a significant benefit in terms of overall and relapse-free survival in multicenter randomized United States cooperative group and intergroup trials. These facts suggest that we have much to do in both patient and physician education and in development of better therapies for melanoma. Richtig et al report in this issue of the Journal of Clinical Oncology the closure of the European Cooperative Adjuvant Melanoma Treatment Study Group (ECAMTSG) placebocontrolled trial of isotretinoin and low-dose IFN compared with low-dose IFN in patients with resected stage IIA and IIB melanoma. Unfortunately, like many other recent trials of adjuvant therapy for melanoma, this trial was closed and reported early when an interim analysis demonstrated no significant likelihood of reaching the initial study goals (1.3%). With this negative experience, and a series of other negative trials recently reported in the literature or in abstracts, it is time to ask the question, How may progress be accelerated and the pitfalls of past trials avoided in future melanoma studies? The potential answers to this complex question may be found in our increasing understanding of the requirements of adjuvant clinical trial design and our scientific understanding of tumor progression, along with an analysis of current effective therapies. Only one adjuvant therapy has stood the test of time: the high-dose IFN -2b regimen tested initially in the Eastern Cooperative Oncology Group E1684 trial and reassessed in the United States intergroup E1690 and E1694 trials reported in the Journal of Clinical Oncology in 1996, 2000, and 2001. These trials have taught us many things, including the importance of prognostic factors for melanoma outcome and the necessity of concurrently randomized controlled trials for rigorous assessment of new interventions. They also point to the large time window between new trial initiation and the return of meaningful answers regarding disease-free and overall survival. The evolution of prognostic factors between trial cohorts, even when trial entry criteria have been relatively consistent in the United States cooperative groups, argues for standardization of major prognostic variables as far as is possible to optimize detection of differences related to experimental interventions. Trials conducted in the recent past have taught us that only robust trials that include sufficient numbers of patients to have the power to arrive at unequivocal conclusions are worthy of our patients’ involvement. The design of clinical trials depends on the anticipated rate of relapse and mortality for the population to be treated: the lower the risk of the group selected, the larger the number of patients needed to answer the trial question. Events among patients with resected stage IIIB to IV disease exceed those for stage IIIA and those, in turn, exceed those for stage IIB and IIA. The numbers required for trials designed to detect clinically relevant differences for survival and progression-free interval increase from 600 to 800 for stage IIIB to IV to numbers that may exceed 1,400 for stage IIIA and stage IIA/B disease. The ECAMSTG study JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 23 NUMBER 34 DECEMBER 1 2005

Safety and toxicity profile of high-dose IFN-α2b in 44 patients with malignant melanoma

7570 Background: High-dose IFN-α2b (HDI) is the only approved adjuvant therapy for high-risk melanoma, while lower dose IFN appears ineffective. Toxicity was substantial in patients (pts) enrolled ...

Safety and toxicity profile of high-dose IFN-α2b in 44 patients with malignant melanoma

7570 Background: High-dose IFN-α2b (HDI) is the only approved adjuvant therapy for high-risk melanoma, while lower dose IFN appears ineffective. Toxicity was substantial in patients (pts) enrolled ...