Cases Of Second Primary Malignancy Research Articles

Screening Adherence for Second Primary Malignancies in Breast Cancer Survivors: Behaviors, Facilitators, and Barriers to Enhance Quality Care

Due to genetic, hormonal, and environmental factors, alongside increased life expectancy, breast cancer (BC) survivors have an increased risk of developing a second primary malignancy. Therefore, regular screening for other types of cancer is of utmost importance for their comprehensive care. This cross-sectional study evaluated BC survivors’ compliance with cervical, lung, and colorectal cancer screening, and identified facilitators and barriers influencing adherence. Fifty-two BC survivors answered the study's survey. A total of three (6%) cases of second primary malignancies were self-reported. Cervical cancer screening was performed within the past 3 years among 37/50 (74%) eligible participants. Only 7/24 (29%) eligible participants underwent colorectal cancer screening within the last 10 years, including six colonoscopies and 1 occult blood test. No participant had an indication for lung cancer screening. The primary reason for noncompliance with both cervical and colorectal cancer screening was lack of physician's recommendation, accounting for 79% and 88% of cases, respectively. Nearly all participants (98%) affirmed that BC survivors should undergo screening for other types of cancer. Most (96%) stated that, if recommended by a physician, they would agree to undergo screening for other neoplasms. Even though most BC survivors acknowledged its importance, screening particularly for colorectal cancer exhibited suboptimal rates. Oncologists could play a crucial role in increasing cancer screening uptake by reminding patients of their corresponding recommendations to detect other types of cancer.

Hematological Second Primary Malignancy in Pediatric Retinoblastoma: A Case Report and Systematic Review.

The impact of heredity and treatment modalities on the development of hematologic second primary malignancies (SPMs) is unclear. This study primarily reviewed the literature on patients with hematologic SPMs after retinoblastoma. The PubMed and Web of Science databases were searched to identify all cases of hematologic SPMs after retinoblastoma through December 2023 (International prospective register of systematic reviews CRD42023488273). Sixty-one patients from 35 independent publications and our case were included. Within the cohort, 15 patients (51.7%) were male, and 14 patients (48.3%) were female. Of the 43 cases with known heritability status, 27 (62.8%) were classified as heritable and 16 (37.2%) as nonheritable. The median age at diagnosis was 18 months (IQR: 7.00-36.00). The geographic distribution of patients was diverse, with North America accounting for 35.0% (21/60) of cases. The following treatment strategies were used: 11.9% (5/42) of patients received neither chemotherapy nor radiotherapy, 33.3% (14/42) received chemotherapy alone, 11.9% (5/42) received radiotherapy alone, and 42.9% (18/42) received a combination of chemotherapy and radiotherapy. The median delay between retinoblastoma diagnosis and SPM diagnosis was 40 months (IQR: 22.00-85.00). Among the 61 cases, acute myeloid leukemia accounted for 44.3% (27/61), followed by acute lymphoblastic leukemia in 21.3% (13/61), Hodgkin's lymphoma in 11.5% (7/61), non-Hodgkin's lymphoma in 9.8% (6/61), chronic myeloid leukemia in 3.3% (2/61), and acute natural killer cell leukemia in 1.6% (1/61). Vigilant systemic surveillance for hematologic SPMs in retinoblastoma survivors, especially those treated with systemic chemotherapy and those with hereditary conditions, is warranted to improve management strategies and patient outcomes.

Incidence and mortality of second primary malignancies after lymphoma: a population-based analysis

Background: Second primary malignancies (SPMs) account for an increasing proportion of human malignancies. We estimated the incidence, risk factors and outcomes in lymphoma survivors with SPMs. Methods: Patients diagnosed with SPMs after primary lymphoma from 2010 to 2021 were included in this study. The incidence, mortality and clinical characteristics of SPMs in our center and Surveillance, Epidemiology, and End Results database were delineated and analyzed. Standardized incidence ratio quantified second cancer risk. Results: A total of 2912 patients of lymphoma were included, 63 cases of SPM met the inclusion criteria, with the prevalence of SPMs after lymphoma was 2.16%. The male-to-female ratio of 2.32:1. The majority of these patients were older (≥60 years old, 61.90%) and previously treated with chemotherapy (68.25%). The common types among SPMs were digestive system tumors (42.86%), respiratory system tumors (20.63%) and urinary system tumors (12.70%). Additionally, cancer risks were significantly elevated after specific lymphoma though calculating the expected incidence. In terms of mortality, the diagnosis of SPMs was significantly associated with an increased risk of death over time. Moreover, although the outcome was favorable in some SPM subtypes (thyroid and breast cancer), other SPMs such as stomach and lung tumors had a dismal prognosis. Conclusion: With the improvement of medical standards, the survival of lymphoma patients has been prolonged. However, the incidence of SPM is increasing, particularly among men and older lymphoma survivors. Therefore, more attention should be invested in the SPM to further improve the prognosis of these patients.

Long-Term Outcomes of Autologous Stem Cell Transplantation in Patients with Newly Diagnosed POEMS Syndrome

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare form of plasma cell dyscrasia often treated with high-dose chemotherapy and autologous stem cell transplantation (ASCT). ASCT has resulted in satisfactory and sustained therapeutic outcomes. However, a substantial number of patients eventually experience disease progression, requiring second-line treatment. Therefore, it would be of further benefit to identify patients who will acquire the best long-term survival after ASCT. The aim of this study was to fully reveal the outcomes of patients undergoing ASCT in a large series with long-term follow-up. Long-term outcomes of 239 patients with newly diagnosed POEMS syndrome undergoing ASCT at a single center were evaluated retrospectively. Rates of hematologic complete response (CRH) and vascular endothelial growth factor (VEGF) complete response (CRV) were 57.3% and 68.6%, respectively, with 90.5% of patients achieving an overall clinical response. At a median follow-up of 94 months, the 5-year overall survival (OS) rate was 92.8%, and the 5-year time to next-line treatment (TTNT) rate was 72.2% (median TTNT, 96 months). Patients achieving CRH (5-year TTNT rate, 82.5% versus 60.7%; P < .0001) or CRV (5-year TTNT rate 83.7% versus 54.2%; P < .0001) had better survival outcomes compared to non-CR group patients. Dual hematologic and VEGF complete responses carry further benefit for survival (median TTNT, 129 months versus 68 months; P < .0001). Seven cases of second primary malignancy were recorded, all of which were solid tumors. Front-line ASCT resulted in excellent long-term survival in patients with POEMS syndrome, with the best survival observed in those achieving dual hematologic and VEGF CRs.

Immunotherapy with PD-1 Inhibitor Nivolumab in Recurrent/Metastatic Platinum Refractory Head and Neck Cancers-Early Experiences from Romania and Literature Review.

Prognosis in recurrent/metastatic head and neck squamous-cell carcinoma (HNSCC) refractory to platinum-based chemotherapy is poor, making therapy optimization a priority. Anti-programmed cell death protein 1 (anti-PD-1) monoclonal antibody Nivolumab was approved in such cases. We present the early experience with Nivolumab immunotherapy at three cancer clinics from south and northeast Romania, aiming to describe the main characteristics and outcomes relative to literature reports, and to suggest patient selection criteria. Diagnostic, clinical, biological, therapeutic, and outcomes-related data from January 2020 until March 2023 were analyzed retrospectively. Eighteen patients with platinum refractory HNSCC (85.7% men, median age 58.9) were administered Nivolumab for 1-14 months (median 5.6 months) in addition to other treatments (surgery, radiotherapy, chemotherapy), and monitored for up to 25 months. Median neutrophil-to-lymphocyte ratio (NLR) ranged from 2.72 initially to 6.01 during treatment. Overall survival (OS) was 16 months, and patients who died early had the sharpest NLR increases (13.07/month). There were no severe immune-related adverse events. Lower NLR values and combined intensive chemotherapy, radiotherapy, and immunotherapy were related to better outcomes. To our knowledge, we also report the first two cases of second primary malignancy (SPM) in the head and neck region treated with Nivolumab in Romania (for which the sequential administration of radiotherapy and immunotherapy seems better). The work of other Romanian authors on the role of HPV status in HNC is also discussed. Multi-center trials are needed in order to investigate and confirm these observations.

CARTITUDE-1 final results: Phase 1b/2 study of ciltacabtagene autoleucel in heavily pretreated patients with relapsed/refractory multiple myeloma.

8009 Background: Heavily pretreated patients (pts) with relapsed/refractory multiple myeloma (RRMM) treated with standard of care therapy have median overall survival (OS) of ~12 months (mo). In the single-arm, phase 1b/2 CARTITUDE-1 study (NCT03548207), pts received a single infusion of ciltacabtagene autoleucel (cilta-cel), a CAR-T cell therapy targeting BCMA. At the final protocol-specified analysis (27.7-mo median follow-up [MFU]), overall response rate (ORR) was 98%, with 83% stringent complete response (CR); 27-mo rates of progression-free survival (PFS) and OS were 55% and 70%, respectively. Here, we report study closeout results. Methods: Eligible pts received ≥3 prior lines of therapy (LOT) or were double refractory to a proteasome inhibitor (PI) and immunomodulatory drug (IMiD); and had received prior PI, IMiD, and anti-CD38 antibody therapy. Primary endpoint was ORR and safety; secondary endpoints included PFS, OS, and minimal residual disease (MRD) negativity at 10-5. Results: 97 pts received cilta-cel (median age 61 years [y]; median 6 prior LOT; 42% penta-drug refractory; 88% triple-class refractory; 99% refractory to last LOT). As of October 14, 2022, MFU was 33.4 mo (range, 1.5-45.2). Median (m) duration of response was 33.9 mo (95% CI, 25.5–not estimable [NE]). mPFS was 34.9 mo (95% CI, 25.2–NE), with an estimated 47.5% progression free and alive at 36 mo. mOS was not reached (NR), with an estimated 62.9% survival at 36 mo. Of 49 MRD-evaluable pts, 26 had MRD negativity sustained for ≥12 mo, of which 20 had sustained MRD-negative ≥CR. mPFS was NR in these subgroups (Table). 18 pts were MRD negative with ≥CR at 24 mo post infusion. No new safety signals and no new neurotoxicity events were reported since the 27.7-mo MFU. 6 new cases of second primary malignancy were reported, including 2 cases of basal cell carcinoma and 1 case each of myelodysplastic syndrome, B-cell lymphoma, melanoma, and prostate cancer. 5 additional deaths occurred (progressive disease [PD], n=3; pneumonia and sepsis, n=1 each [both unrelated to cilta-cel]), for a total of 35 (PD, n=17; unrelated to cilta-cel, n=12; related, n=6). Conclusions: Longer mPFS was observed after a single infusion of cilta-cel than any previously reported therapy in heavily pretreated pts with RRMM. Achieving CR and/or sustained MRD negativity was associated with prolonged PFS. Pts continue to be followed for safety and survival in the 15-y CARTINUE long-term study (NCT05201781; MMY4002). Clinical trial information: NCT03548207 . [Table: see text]

Treatment of Early-Stage Nodular Lymphocyte-Predominant Hodgkin Lymphoma: A Subgroup Analysis of the Randomized German Hodgkin Study Group HD16 Study

Background:Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma entity accounting for approximately 5% of all Hodgkin lymphoma (HL) cases. Pathological and clinical characteristics differ from classical HL (cHL). In contrast to cHL, the malignant cells in NLPHL are consistently positive for CD20 but stain negative for CD30. The clinical course of NLPHL is usually indolent and patients present with early-stage disease more frequently than in cHL.Patients and Methods:We investigated characteristics and outcomes of 85 patients with NLPHL (stage IB and stage II without risk factors) who had treatment within the randomized German Hodgkin Study Group HD16 study for early-stage HL. Results were compared to those from 495 cHL patients (stage IB and stage II without risk factors) treated within the same study. Patients were randomized between standard treatment consisting of 2 cycles of ABVD followed by consolidation radiotherapy and treatment guided by interim positron emission tomography after 2 cycles of ABVD (PET-2). PET-2-guided treatment consisted of 2 cycles of ABVD alone for patients with a negative PET-2 and 2 cycles of ABVD followed by consolidation radiotherapy for patients with a positive PET-2 (defined as a Deauville score ≥ 3). Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method including 95%-confidence intervals (95%-CI) and hazard ratios (HR) obtained from Cox regression models. Analyses were performed descriptively.Results:Overall, 62/85 NLPHL patients (73%) were male as compared to 254/495 cHL patients (51%) (p=0.0002). The median age was 37 years (range: 19-71 years) among patients with NLPHL and 36 years (range: 18-75 years) among patients with cHL (p=0.4380). Information on the histopathological growth pattern was available for 67/85 NLPHL patients of which 44 (66%) had a typical growth pattern. The PET-2 was positive in 39/85 NLPHL patients (46%) and in 171/495 cHL patients (35%) (p=0.0507). After a median observation time of 64 months, the 5-year PFS was 90.3% (95%-CI: 83.8-96.7%) for all 85 NLPHL patients and 90.8% (95%-CI: 88.1-93.5%) for all 495 cHL patients (HR=1.1; 95%-CI: 0.5-2.1). The 5-year PFS rates for PET-2-positive NLPHL (n=39) and cHL (n=171) patients were 89.3% (95%-CI: 79.4-99.2%) and 91.6% (95%-CI: 87.2-96%) (HR= 1.3; 95%-CI: 0.5-3.5), respectively. The 5-year PFS rates for PET-2-negative NLPHL (n=46) and cHL (n=324) patients were 91% (95%-CI: 82.7-99.4%) and 90.4% (95%-CI: 87-99.4%) (HR=0.85; 95%-CI: 0.3-2.4), respectively. PET-2-negative NLPHL (n=25) and cHL (n=152) patients treated with 2 cycles of ABVD alone had 5-year PFS rates of 83% (95%-CI: 67.8-98.2%) and 88.2% (95%-CI: 82.7-93.6%) (HR=1.5, 95%-CI: 0.5-4.5), respectively. In contrast, PET-2-negative NLPHL (n=21) and cHL (n=172) patients treated with 2 cycles of ABVD followed by consolidation radiotherapy had 5-year PFS rates of 100% and 92.3% (95%-CI: 88.1-96.5%) (HR=0; 95%-CI: 0), respectively. NLPHL patients with a typical growth pattern (n=44) had a 5-year PFS of 95.2% (95%-CI: 88.8-100%) whereas patients with an atypical growth pattern (n=23) had a 5-year PFS of 82.2% (95%-CI: 66.3-98%) (HR=2.5; 95%-CI: 0.5-11.2). A total of 9 NLPHL patients experienced disease progression or relapse during follow-up. The median time to NLPHL recurrence was 14 months (range: 1-89 months). There were 2 cases of second primary malignancies (1 case of malignant melanoma, 1 case of stomach cancer) among patients with NLPHL. No patient developed histological transformation into aggressive B-cell non-Hodgkin lymphoma. The 5-year OS rates were 100% and 98.6% (95%-CI: 97.5-99.7%) (HR=0; 95%-CI: 0) for patients with NLPHL and cHL, respectively.Conclusion:Taken together, the 5-year outcomes for patients with newly diagnosed early-stage NLPHL were similar to their counterparts with cHL. Thus, the current standard of care for early-stage cHL consisting of 2 cycles of ABVD followed by consolidation radiotherapy represents a highly active option also for the treatment of patients with the initial diagnosis of stage IB and stage II NLPHL without risk factors. DisclosuresFuchs: Takeda: Consultancy, Honoraria; Lukon: Honoraria; Celgene: Honoraria; BMS: Honoraria; MSD: Honoraria. von Tresckow: AstraZeneca: Honoraria, Other: congress and travel support; Kite-Gilead: Consultancy, Honoraria; BMS-Celgene: Consultancy, Honoraria, Other: congress and travel support; Amgen: Consultancy, Honoraria; AbbVie: Other: congress and travel support; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: congress and travel support, Research Funding; Pentixafarm: Consultancy, Honoraria; MSD: Consultancy, Honoraria, Other: congress and travel support, Research Funding; Roche: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other, Research Funding. Engert: Takeda: Consultancy, Honoraria, Research Funding; BMS: Honoraria, Research Funding; Astra Zeneca: Consultancy, Honoraria; Tessa Therapeutics: Consultancy; Amgen: Honoraria; ADC Therapeutics: Consultancy; MSD: Honoraria; Hexal: Honoraria.

Second Primary Malignancy after Acute Promyelocytic Leukemia: A Population-Based Study.

Simple SummaryAcute promyelocytic leukemia (APL) is a rare and aggressive subtype of acute myeloid leukemia (AML). Since the introduction of all-trans-retinoic acid (ATRA) in APL management, the survival rate has increased substantially. However, there is evidence that retinoids might enhance tumor growth and the risk of secondary malignancies. The relationship between secondary cancer risk and APL treatment that includes ATRA is incompletely characterized. In this study, we investigated the risk factors associated with second primary malignancies after treatment of APL. Age ≥ 40 years at diagnosis of APL was significantly associated with an increased risk of second malignancies. Our findings suggest a potential carcinogenic role for ATRA in the salivary gland, liver, and soft tissue malignancies. Moreover, secondary tumors were significantly more frequent among patients with primary APL than in individuals with non-APL malignancies. Our finding suggests opportunities for surveillance for patients who completed treatment for APL.Acute promyelocytic leukemia (APL), is now highly curable with treatment approaches that include all-trans retinoic acid (ATRA). The high incidence of APL in the Hispanics suggests an association with genetic variants in this population. Information on second primary malignancies (SPMs) in patients with APL is limited. The Surveillance, Epidemiology, and End Results (SEER) database was used to interrogate whether the rate of SPMs in patients with APL was associated with ethnicity and/or ATRA treatment. Between 2000 and 2016, 116 cases of SPM were diagnosed among 4019 patients with APL. The mean age at diagnosis of primary APL was 53.9 years (±15.7 years), and the mean age at diagnosis of SPMs was 59.0 years (±14.5 years). Comparisons with 3774 APL survivors who did not develop SPMs revealed that age ≥40 years at diagnosis of APL (p < 0.001) and non-Hispanic white ethnicity (p = 0.025) were associated with SPMs in APL survivors. Salivary gland, liver, and soft tissue malignancies were significantly more common in patients with primary APL than in individuals with non-APL malignancies. A risk analysis comparing patients who had APL with patients who had non-APL AML suggests that SPMs after APL is associated with ATRA treatment. Therefore, patient follow-up after APL should focus on early diagnosis of SPMs.

The impact of primary tumor location (PTL) and age on the risk of developing noncolonic second primary malignancy (SPM) in colon cancer (CC) patients (PTS).

67 Background: Colon cancer remains one of the leading causes of cancer death worldwide. There has been a renewing interest in the role of PTL (right- or RS vs. left-sided or LS) in CC for their differences in biology, prognostic and predictive features. Given the increasing incidence of early-onset (age 20-49) CC, coupled with their longer life expectancy, we seek to examine the effects of PTL and age in the development of SPM in a population-based cohort. Methods: Surveillance, Epidemiology, and End Results (SEER) Program data were queried to identify CC PTS diagnosed between 1973-2015 with complete follow-up information and available data on SPM. Using SEER*Stat, we calculated standardized incidence ratios (SIRs) -- the ratio of observed to expected cases of SPM based on incidence data in the general US population and compared by PTL (RS vs. LS) and age of diagnosis (20-49 vs. &gt;49). Results: A total of 269,442 (RS/LS=46.4%/53.6%) CC PTS were obtained. Overall RS, compared with LS, CC PTS have a higher likelihood of developing SPM in all sites (OR: 1.09, 95% CI: 1.08- 1.11 vs. 1.03, 1.02-1.04). RS CC PTS and age 20-49 group, compared with other subgroups, has a much greater likelihood of being diagnosed with the following SPM:small intestine, urinary tract, bile duct, gynecologic (GYN), and stomach cancers, as shown in the Table below. Conclusions: Our results show that the increased risk in non-colonic SPMs in CC PTS is associated with RS CC and age less than 49, suggesting the implications on survivorship care and surveillance of SPMs. Furthermore, there may be a possible overlap with Lynch syndrome in these PTS with SPM given the overlap in the presentation of cancer patterns and early-onset of CC, suggesting the indication for MMR testing. [Table: see text]

PS1462 SECOND PRIMARY MALIGNANCIES IN MYELOFIBROSIS PATIENTS TREATED WITH RUXOLITINIB: REAL WORLD EVIDENCE FROM 215 CONSECUTIVELY TREATED PATIENTS IN LOMBARDY

Background:Patients with myeloproliferative neoplasms (MPNs) have a higher risk than the general population of developing a lymphoid neoplasm (Rumi et al, Haematologica 2011). It is still unclear whether this holds true for non‐hematological second primary malignancies (SPMs) (Frederiksen et al, Blood 2011; Susini et al, Blood 2012). However, among 20,250 MPN patients included in the Surveillance, Epidemiology, and End Results Program (SEER) database, the 10‐year cumulative incidence of SPMs was 12.7%, significantly higher than that expected in the general U.S. population (Brunner et al, Leuk Lymphoma 2016). Ruxolitinib (RUX) is an oral JAK1/2 inhibitor approved for the treatment of myelofibrosis (MF). Recently, Porpaczy et al (Blood 2018) alerted on the possible risk of aggressive lymphomas developing in MPN patients treated with JAK inhibitors including RUX, even though patient selection bias complicates interpretation.Aims:To assess SPM occurrence in RUX‐treated MF patients on the basis of real world data (RWD) provided by the health authority of Regione Lombardia, complemented with institutional data.Methods:Lombardy, a region of roughly 10 million individuals, has a well‐established network for hematology (Rete Ematologica Lombarda, REL), with a specific commission for MPNs. Within the REL we conducted an ambispective observational study (RUXOREL‐MF) including all MF patients treated with RUX, i.e. 215 subjects regularly followed at 17 centers. The study was approved by the Review Board of each Institution and conducted in accordance with the Declaration of Helsinki. Incidence rates were computed from the number of events versus the time at risk after RUX start. Time‐to‐event analyses used Kaplan‐Meier estimators, log‐rank tests and cause‐specific Cox models based on time elapsed after RUX start.Results:Main patient characteristics according to SPM (excluding non‐melanoma skin cancer, NMSC) occurrence are summarized in Table 1. Median follow up from diagnosis of MF was 61.5 months (interquartile range, IQR, 34.1–97.3). Median follow up from RUX start was 24.2 months (IQR 12.6–40.4). Forty‐nine (22.8%) patients died, two due to the SPM. Median overall survival from RUX start was 78.7 months. 27 cases of SPMs were reported prior to RUX start, with no case of lymphoma. 24 cases of SPMs occurred after RUX start (lung, 1; breast, 3; prostate, 2; bladder, 1; melanoma, 1; multiple myeloma, 1; NMSC, 13; other, 2). The incidence rate of SPMs post‐RUX was 4.3 per 100 pt‐years (95% CI 2.7–6.5), whereas it was 1.7 per 100 pt‐years (95% CI 0.8–3.2), when excluding NMSCs from the analysis. Median time to SPM diagnosis after RUX start was 16.9 months (IQR 6.9–21.5) and 19.8 months (IQR 16.3–36.7) when excluding NMSCs. Cumulative incidence of SPMs (excluding NMSCs) after RUX start is reported in Fig. 1. Patients with a SPM pre‐RUX were at higher risk of developing a SPM post‐RUX (HR 3.6, 95% CI 1.1–11.0, p = 0.02). Significance was lost if the analysis excluded NMSC (HR 3.8, 95% CI 0.8–18.7, p = 0.08).Summary/Conclusion:Our RWD offer a unique opportunity to provide real world evidence on the incidence of SPMs in MF patients receiving RUX. In our cohort no case of lymphoma was registered with a median follow up after RUX start matching the median time to lymphoma occurrence reported in the aforementioned publication. Incidence of SPMs after RUX start was 4.3 per 100 pt‐years and 1.7 per 100 pt‐years when excluding NMSC. A matched control study including MF patients not receiving RUX is ongoing and will be presented at the EHA meeting.image

Comparison of Autologous Hematopoietic Cell Transplant (autoHCT), Bortezomib, Lenalidomide (Len) and Dexamethasone (RVD) Consolidation with Len Maintenance (ACM), Tandem Autohct with Len Maintenance (TAM) and Autohct with Len Maintenance (AM) for up-Front Treatment of Patients with Multiple Myeloma (MM): Primary Results from the Randomized Phase III Trial of the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0702 -

Background: Len maintenance after autoHCT has improved progression-free (PFS) and overall survival (OS). However, the role of additional interventions after autoHCT such as tandem autoHCT or triple therapy consolidation remains to be determined.Methods: This is a phase III clinical trial (NCT#01109004) of transplant-eligible patients (pts) with symptomatic MM <71 years of age within 12 months of initiating therapy and without prior progression who were randomly assigned 1:1:1 to receive melphalan 200mg/m2 autoHCT and 4 cycles of RVD consolidation (lenalidomide 15mg daily days 1-14, dexamethasone 40mg day 1,8 and 15, and bortezomib 1.3mg/m2 days 1,4,8 and 11 every 21 days) (ACM), versus tandem melphalan 200mg/m2 autoHCT (TAM) or versus a single autoHCT (AM). Randomization was stratified by disease risk (cytogenetic abnormalities - del13q by karyotype, del17q, t(4;14), t(14;16), t(14;20) and hypodyploid; or high beta-2 microglobulin) and center. All arms included Len maintenance (at maximum tolerated dose of 5 to 15 mg orally daily until progression) with dose modifications for toxicities. All patients were reviewed centrally for eligibility, response and progression. The primary objective was to compare 38-month PFS of the three arms. The events for PFS included progression, non-protocol anti-myeloma therapy, or death. Comparisons between treatment groups were based on pairwise log-rank tests stratified on disease risk, with significance levels adjusted for the 3 pairwise comparisons and for interim analyses. In calculating the cumulative incidence of progression, the events were progression or non-protocol anti-myeloma therapy, and death was a competing risk.Results: From June 2010 to November 2013, 758 pts (ACM, N=254; TAM, N=247; AM, N=257) aged 20-70 years (median 57y) were enrolled. Of those enrolled, 24% were classified as high risk. Non-compliance rates following the first autoHCT were 12%, 32% and 5% for ACM, TAM and AM, respectively. Median available follow up from randomization was 38 months. Follow-up is continuing through January 2017. 38-month estimated probabilities for PFS were 57% (95% CI: 50-63%), 56% (95% CI: 49-63%) and 52% (95% CI: 45-59%) for ACM, TAM and AM, respectively (ACM vs TAM p=0.75, ACM vs AM p=0.21, TAM vs AM p=0.37). Corresponding probabilities of OS were 86% (95% CI: 80-90%), 82% (95%CI: 76-87%) and 83% (95% CI: 78-88%). Median OS has not been reached. Cumulative incidences of disease progression at 38 months were 42% (95% CI: 36-48%), 42% (95% CI: 35-48%) and 47% (95% CI: 40-54%) for the ACM, TAM and AM arms, respectively. There were 39 cases of second primary malignancy (SPM) reported in 36 participants and the cumulative incidences for first SPM were 6.0% (95% CI: 3.4-9.6%), 5.9% (95% CI: 3.3-9.6%) and 4.0% (95% CI: 1.9-7.2%) for the ACM, TAM, and AM, respectively.Conclusions: The primary results of the largest randomized US transplant trial in MM demonstrated comparable PFS and OS. The addition of RVD consolidation or a second auto-HCT was not superior to a single auto HCT followed by Len maintenance in the upfront treatment of MM. A long term follow-up trial to track outcomes in these patients is ongoing. DisclosuresStadtmauer:Amgen: Consultancy; Takeda: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Janssen: Consultancy. Pasquini:Atara: Other: travel reimbursement for a meeting; Baxalta: Honoraria, Membership on an entity's Board of Directors or advisory committees. Efebera:Millennium/Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Honoraria. Ganguly:Onyx: Speakers Bureau; Seattle Genetics: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees. Giralt:Celgene: Consultancy; Millenium/Takeda: Consultancy. Hari:Celgene: Consultancy; Millennium/Takeda: Consultancy. McCarthy:Celgene: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Millennium/Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; The Binding Site: Consultancy, Honoraria. Qazilbash:Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Shah:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium/Takeda: Membership on an entity's Board of Directors or advisory committees. Vesole:Takeda: Speakers Bureau; Celgene: Speakers Bureau. Vij:Millennium/Takeda: Consultancy; Celgene: Consultancy. Vogl:Celgene: Consultancy; Millennium/Takeda: Consultancy, Research Funding. Somlo:PUMA: Consultancy; Abbvie: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium/Takeda: Speakers Bureau; Astra Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees. Krishnan:Celgene: Consultancy, Speakers Bureau; Millennium/Takeda: Consultancy, Speakers Bureau; Onyx: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau.

Risk of Second Non-Breast Primary Cancer in Male and Female Breast Cancer Patients: A Population-Based Cohort Study.

Female breast cancer patients have an increased risk of developing subsequent malignant diseases, but this issue is rarely discussed in regards to male breast cancer patients. Thus, we conducted a national survey that included 100,915 female and 578 male breast cancer patients to investigate the risk of second primary malignancy (SPM). During a follow-up period that included 529,782 person-years, 3,153 cases of SPM developed. Compared with the general population, the standardized incidence ratio (SIR) of SPM in breast cancer patients was 1.51 [95% confidence interval (CI): 1.46–1.56]. The observed risk was significantly higher in male patients (SIR 2.17, 95% CI 1.70–2.73) and in patients whose age at breast cancer diagnosis was 40 years or younger (SIR 3.39, 95% CI 2.80–4.07), comparing to age-matched general population. Compared with the overall female population, the SIRs of female breast cancer patients with uterine (SIR: 2.66, 95% CI: 2.37–2.98), thyroid (SIR: 2.30, 95% CI: 2.02–2.62), and bone and soft tissue (SIR: 2.16, 95% CI: 1.56–2.91) cancers were significantly increased. Male breast cancer patients also displayed significantly higher SIRs for thyroid (SIR: 13.2, 95% CI: 1.60–47.69), skin (SIR: 8.24, 95% CI: 3.02–17.94) and head and neck (SIR: 4.41, 95% CI: 2.35–7.54) cancers. Among breast cancer patients, risk factors significantly associated with SPM included male gender, older age, chemotherapy treatment and comorbidity with liver cirrhosis. From our analysis, we concluded that the risk of SPM was significantly higher for both male and female breast cancer patients compared with the general population, suggesting that more intensive surveillance may be needed, especially in high-risk patients.

Second primary malignancy: A retrospective analysis report from a tertiary cancer center of North India.

We analyzed the data of second primary malignancy (SPM) from one of the tertiary cancer centers of North India, and the basic aim was to retrieve incidence, prognosis, and outcomes. A retrospective study was conducted in the Department of Radiation Oncology in a tertiary cancer center between January 1, 2011, and December 31, 2015. A total of 6000 cases of cancer were analyzed, out of which cases who presented with histological proven synchronous SPM were included in this study. The present study showed three cases (8.1%) of SPM who are attributed to field carcinogenesis. There were five cases in which metachronous malignancy develops in the previous radiation therapy field. There is 26% of synchronous malignancy as compared to 74% of metachronous malignancy. In the present study, most diagnosed synchronous malignancies were carcinoma breast, while in metachronous malignancies, carcinoma breast and gynecological cancers were most common. SPMs are not very rare. Hence, pretreatment and follow-up evaluation should be meticulous to rule out SPMs.

Autopsy Analysis may Contribute to Establish Actual Incidence of Second Primary Malignancies in Myeloma.

Second primary malignancies (SPMs) are issues for patients with multiple myeloma (MM). There may have been some limitations in prior studies, such as difficulties in a longer follow-up and absence of established screening methods. Therefore, we studied autopsied cases to overcome these limitations. This study aimed to examine SPMs using autopsy reports. Ninety-one cases of MM autopsied at our institution from 1979 to 2013 were analyzed. Median age of autopsied patients was 64.1 years, and proportion of male/female was 59/32. Autopsy was performed in 35.3% of patients died of MM. There were five cases of SPMs with a median confirmation time of 38 (12-132) months from the diagnosis of MM. In three of the five patients, the diagnosis of SPMs was established at autopsy. One case was of myelodysplastic syndrome, and the others were of non-hematological malignancies. The annual risk of SPM estimated using the Kaplan-Meier method was approximately 1%. Three of five SPM cases were detected at autopsy. Analysis of autopsy may contribute to estimate the actual risk of SPMs in MM.

The risk of second primary cancers in clear cell and papillary renal cancer.

446 Background: Renal cell carcinoma (RCC) survivors have an increased risk of developing second primary cancers. We sought to determine the role of RCC tumor histology for the risk of developing second primary solid tumors. Methods: The Surveillance Epidemiology and End Results (SEER) database was used to detect RCC cases diagnosed up to 12/31/2011. The Standardized Incidence Ratio (SIR) was calculated as the ratio of observed to expected cases of second primary malignancy based on incidence data in the general United States population. The two most common RCC histological subtypes were included; clear cell and papillary. The latency exclusion period from the date of diagnosis was 60 months. We investigated for the effect of latency period after initial diagnosis (5-10 years and &gt;10 years) that may increase the risk for a second primary cancer. Results: A total of 2,669 patients with an initial diagnosis of RCC (clear cell: 2,368, papillary: 301) that developed second primary cancers were included in our analysis. There was a significantly increased risk of thyroid cancer (SIR: 2.30, p&lt;0.05), prostate cancer (SIR: 1.12, p&lt;0.05) and “all solid tumors” (SIR: 1.14, p&lt;0.05) in clear cell RCC cases. Regarding latency period, thyroid cancer (SIR: 2.87, p&lt;0.05) risk was increased in the 5-10 years latency period, but not in the &gt;10 years latency period. Overall, in patients diagnosed with papillary RCC, tumors of the prostate (SIR: 1.30, p&lt;0.05), lung (SIR: 1.78, p&lt;0.05) and pancreas (SIR: 2.70, p&lt;0.05) were increased. Exclusively in the 5-10 years latency period, the risk for developing lung cancer (SIR: 1.90, p&lt;0.05) was significant. Conclusions: RCC histology may impact the risk for developing specific second primary solid tumors.

Second primary cancers in young adult colorectal cancer survivors.

516 Background: Second primary cancers are a major concern for young adult colorectal cancer (CRC) survivors. The impact of treatment with radiation on the risk for second solid and hematological malignancies, as well as the typical latency period before development of a second cancer, requires elucidation. Methods: The Surveillance Epidemiology and End Results (SEER) database was used to detect CRC cases in young adults (aged 20-40 years) diagnosed up to 12/31/2011. The Standardized Incidence Ratio (SIR) was calculated as the ratio of observed to expected cases of second primary malignancy based on incidence data in the general United States population. The latency exclusion period from the date of diagnosis was 5 years. We investigated the possible effect of radiation therapy on risk for a second cancer, and established the typical latency period after initial diagnosis (5-10 years and &gt;10 years). Results: A total of 9,537 cases of CRC in young adults were available for analysis. Radiation was administered in 1,823 (19.1%) patients. Second primary cancers occurred in 798 cases, 754 (94.5%) solid tumors and 44 (5.5%) hematological malignancies respectively. In the latency period 5-10 years after initial diagnosis, “All Solid Tumors” (SIR: 1.85, p&lt;0.05) and female genital tumors (SIR: 3.52, p&lt;0.05) were increased. In the latency period &gt;10 years after initial diagnosis, an increased risk of developing pancreatic cancer (SIR: 1.90, p&lt;0.05) and female genital tumors (SIR: 1.77, p&lt;0.05) was observed. In patients who received radiation the only significantly increased risk was for “All Solid Tumors” (SIR: 1.42, p&lt;0.05). No significant increase in second hematological malignancies was observed in the entire cohort, including cases that received radiation. Conclusions: An increased risk of second primary female genital tumors was seen in both the 5-10 years and &gt;10 years latency periods. Pancreatic cancer risk was increased specifically in the &gt;10 years latency period. Radiation treatment did not pose an increased risk for any specific second primary cancers. Interestingly, young adult CRC survivors did not have an increased risk for hematological malignancies compared to the general population.

Secondary primary cancers in male breast cancer survivors.

129 Background: Male Breast Cancer (MBC) survivors have an increased risk of developing secondary contralateral breast cancer. However, the risk of developing other solid tumors and hematological malignancies is not well understood. Methods: The Surveillance Epidemiology and End Results (SEER) database was used to detect MBC cases diagnosed up to 12/31/2011. The Standardized Incidence Ratio (SIR) was calculated as the ratio of observed to expected cases of second primary malignancy based on incidence data in the general United States population. The latency exclusion period from the date of diagnosis was 5 years. We also investigated for any modifying effects such as radiation therapy, age at diagnosis, and latency period after initial diagnosis (5-10 years and &gt;10 years) that may have increased the risk for secondary cancer. Results: A total of 1,239 men with an initial diagnosis of primary breast cancer were included in our analysis. Overall, there was an increased SIR of secondary solid tumors of the pharynx (SIR: 8.39, P&lt;0.05), hypopharynx (SIR: 15.77, P&lt;0.05), and brain (SIR: 4.40, p&lt;0.05), and Non-Hodgkin Lymphoma (NHL) (SIR: 2.49, P&lt;0.05), that was also seen in MBC cases that received radiation (24.1%), (SIR: 4.51, P&lt;0.05). For MBC diagnoses in patients &gt;40 years, there was an increased incidence for these malignancies and for “all solid tumors” (SIR: 1.30, P&lt;0.05) as well. In the period ranging from 5-10 years after initial breast cancer diagnosis increased incidence for tumors of the pharynx (SIR: 8.95, P&lt;0.05) and hypopharynx (SIR: 16.70, P&lt;0.05) were seen. In contrast, there was no significant increased incidence of secondary cancers &gt;10 years after initial diagnosis. Conclusions: MBC survivors are at increased risk for secondary malignancies of the pharynx, hypopharynx, brain, and NHL. Older age at diagnosis and radiation treatment appear to be risk factors. Risk of secondary tumors of the pharynx and hypopharynx is greatest 5-10 years after initial breast cancer diagnosis but optimal surveillance for MBC survivors requires further clarification.

A Phase 2 Study of Elotuzumab (Elo) in Combination with Lenalidomide and Low-Dose Dexamethasone (Ld) in Patients (pts) with Relapsed/Refractory Multiple Myeloma (R/R MM): Updated Results

A Phase 2 Study of Elotuzumab (Elo) in Combination with Lenalidomide and Low-Dose Dexamethasone (Ld) in Patients (pts) with Relapsed/Refractory Multiple Myeloma (R/R MM): Updated Results

Second Primary Malignancies in Newly Diagnosed Multiple Myeloma Patients Treated with Lenalidomide: Analysis of Pooled Data in 2459 Patients

Abstract 996 Background:The risk of developing a tumor is 2.1% per year of life in the general population older than 65 years. In MGUS, the incidence of AML/MDS is increased 8 fold compared with normal population, this observation supports a role for non-treatment related factors in the causation of AML/MDS in plasma-cell dyscrasias (Blood, July 27,2011). In multiple myeloma (MM) patients, the risk of second primary malignancy (SPM) is influenced by age and the use of alkylating agents. Methods:We examined SPM incidence rates (IRs) per 100 person-years in 2459 newly diagnosed MM patients, enrolled in 9 experimental trials of the European Myeloma Network (RVMM EMN 01, RVMM EMN 441, RVMM PI 026, RVMM PI 302, RVMM PI 209, GIMEMA MM 03 05, GIMEMA MM 04 05, GISMM 2001, HOVON 87). 287 patients received cyclophosphamide-lenalidomide-corticosteroids (CRC), 685 melphalan-prednisone-lenalidomide (MPR), 484 high-dose melphalan followed by lenalidomide maintenance (MEL200-R), 164 melphalan-prednisone (MP), 328 MP-thalidomide (MPT), 257 MP-bortezomib (MPV), 254 MP-bortezomib-thalidomide (VMPT). This post hoc analysis was restricted on pooled data from 1798 patients with at least 1 year of follow-up. Results:As of March 2011 cut-off, median follow-up was 28 months. Median age was 69 years, 49% of patients were aged 65–74 years, and 19% aged ≥75 years. Total cases of SPMs were 30/1798 (IR 0.72), including 8 hematologic (acute leukemia) and 22 solid cancers (gastrointestinal, lung, breast, skin, gynecologic). No cases of SPMs were reported in patients receiving cyclophosphamide and lenalidomide.CRC/MPR (N=534)MEL200-R (N=366)MP/MPT/MPV/VMPT (N=898)Total invasive SPM6717Incidence rate*0.660.870.67Hematologic SPM107Incidence rate*0.1100.28Solid tumor SPM5710Incidence rate*0.550.870.39*Incidence rate per 100 person-years.SPM: second primary malignancy; CRC: cyclophosphamide-lenalidomide-corticosteroids; MPR: melphalan-prednisone-lenalidomide; MEL200-R: high-dose melphalan followed by lenalidomide maintenance; MP: melphalan-prednisone; MPT: MP-thalidomide; MPV: MP-bortezomib; VMPT: MP-bortezomib-thalidomideIn patients receiving lenalidomide and alkylating agents (CRC/MPR/MEL200-R), the cumulative incidence of death for MM and diagnosis of SPMs at 3 years was 13.8% and 2.0%, respectively. In patients not receiving lenalidomide (MP/MPT/MPV/VMPT), the cumulative incidence of death and SPMs at 3 years was 26.1% and 1.1%, respectively. In the analysis restricted to Italian patients treated with lenalidomide and alkylating agents, we report 11 cases of SPMs. This figure is lower than the 15.6 cases expected from the age/sex adjusted incidence derived form the Italian Cancer Registry, with a standardized incidence ratio of 0.70. Conclusions:SPM incidence was lower than expected in all treatment groups. At present, the benefits of continuous therapy with lenalidomide outweigh the potential risk of SPMs. Longer follow-up is needed to definitively assess the risk of SPMs in patients receiving lenalidomide with alkylating agents. With the limitation of a short follow-up, the numbers currently support a role for non-treatment related factors as causes of SPMs. Updated data will be presented at the meeting. Disclosures:Palumbo:Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Merck: Honoraria; Amgen: Honoraria. Larocca:Janssen-Cilag: Honoraria. Zweegman:Celgene: Honoraria, Research Funding; Janssen-Cilag: Honoraria, Research Funding. Musto:Celgene: Consultancy, Honoraria, Research Funding. Lokhorst:Celgene: Consultancy; Genmab: Consultancy. Ria:celgene: Consultancy. Patriarca:Celgene: Honoraria; Schering-Plough: Honoraria. Bringhen:Celgene: Honoraria; Janssen-Cilag: Honoraria; Novartis: Honoraria; Merck Sharp & Dhome: Membership on an entity’s Board of Directors or advisory committees. Hajek:Merk: payment for educational presentation; celgene: Honoraria; Janssen-Cilag: Honoraria. Spencer:Janssen: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Boccadoro:Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Research Funding. Sonneveld:Celgene: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Onyx: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Millennium: Membership on an entity’s Board of Directors or advisory committees.

Site-specific relative risks of second primary malignancies among patients with Waldenstrom macroglobulinemia.

e18566 Background: Waldenstrom Macroglobulinemia (WM) is a rare and indolent B-cell malignancy characterized by overproduction of monoclonal immunoglobulin M protein. The long duration of survival for most patients with WM and the use of potentially carcinogenic agents during therapy raise concerns about the development of second primary malignancies. However, the relative risks of second primary malignancies among patients with WM are not well-documented. Therefore, we investigated site-specific relative risks of second primary malignancies among patients with primary WM. Methods: Data from 9 population-based registries of the Surveillance, Epidemiology, and End Results program were used to identify patients diagnosed with primary WM between 1973 and 2007 for whom follow-up data were available. Standardized incidence ratios (SIRs) with corresponding 95% confidence intervals (CIs) of site-specific second primary malignancies were estimated by dividing the number of observed cases of second primary malignancies for the specific site within the WM cohort by the number of expected cases (standardized by age, sex, race/ethnicity, and calendar-year) of secondary primary malignancies for the specific site in the general United States population. Results: The WM cohort (n=1,521) yielded 226 second primary malignancies during 6,958 person-years of follow-up (incidence density = 3,248 cases/100,000 person-years of follow-up). Potentially durable estimates of higher site-specific relative risks were observed for colon (SIR=2.3, 95% CI: 1.6, 3.3), lung (SIR=1.7, 95% CI: 1.2, 2.4), non-Hodgkin lymphoma (SIR=4.9, 95% CI: 3.2, 7.1), myeloma (SIR=4.9, 95% CI: 2.2, 9.2), and acute myeloid leukemia (SIR=5.9, 95% CI: 2.2, 12.8) compared to the general US population. Conclusions: Our results indicate that patients with WM have a higher relative risk of second primary malignancies for several sites. Although the higher relative risks of second primary hematologic malignancies may be treatment- or immunologically-related, the modestly higher relative risks of second primary solid tumors may be the result of detection bias or risk factors shared between WM and the specific solid tumors.