Saunthararajah, Yogen

Abstract Introduction Population level data about the survival outcomes of patients with hematologic malignancies occurring as second cancers is limited. We undertook one of the largest analyses of second hematologic malignancies (SHM) using the Surveillance, Epidemiology & End Results (SEER) registry to identify factors associated with survival. Methods SEER 9 &13 registries were queried to identify adult patients (pts>18 years) diagnosed with SHM that comprised of Acute Myeloid Leukemia (AML), Acute Lymphoid Leukemia (ALL), Myelodysplastic Syndromes (MDS), Chronic Myeloid Leukemia (CML) & Other Acute Leukemias (OAL, biphenotypic leukemias, myeloid sarcomas & leukemias NOS) > 1 year (yr) after diagnosis of a primary unrelated cancer, using ICD-O-3 codes over a 40 yr period (1973-2012). Data on demographics, follow up, primary tumor & survival were abstracted. Univariate & multivariate analyses were performed to identify factors influencing survival of SHM & compared with hematologic malignancies occurring as first cancers. Hazard ratios (HR) with 95% confidence intervals (CIs) are reported & significance was set at p< 0.01. Results SHM cases included 4665 AML, 3569 MDS, 1140 OAL, 1076 CML & 536 ALL pts. Median age at diagnosis of SHM was 73 yrs (range, 18-100) for AML, 79 yrs (18-100) for MDS, 74 yrs(20-99) for OAL, 74 yrs(18-98) for CML & 70 yrs(19-97) for ALL. Pts>60 yrs comprised 79.2% of AML, 92% of MDS, 88.7% of OAL, 82.9% of CML & 75.2% of ALL cases. Gender distribution was similar across all categories, with females comprising 48.5% of AML, 42.2% of MDS, 45.3% of OAL, 42.8% of CML & 50.2% of ALL cases. More than 85% of pts in each group were Caucasians. While the majority of pts had one primary unrelated cancer (82-89%), 14% of AML pts, 17.8% of MDS pts, 13.8% of OAL, 15.3% of CML pts& 10.6% of ALL pts had >1 primary unrelated cancer. Most common primary sites were prostate (19.1-29.6%), breast (16.1-21.9%) & colorectal (9.3-14.5%). Median survival (range) was as follows: AML 0.2 yrs (0-28.2); MDS 1.5 yrs (0-14); OAL 0.2 yrs (0-29.1); CML 2.5 yrs (0-27.1); & ALL 0.7 yrs (0-28.8). Median latency periods (range) for secondary cancers were as follows: AML 5.2 yrs (1.0-24.2); MDS 7.6 yrs (1.0-35.5); OAL 5.7 yrs (1.0-=34.3); CML 5.2 yrs (1.0-31.6); & ALL 6.2 yrs (1.0-35.5). In univariable analyses, age <60 yrs predicted for better survival (p<0.0001) for all SHM, as did diagnosis in recent yrs (2001-2012) (p< 0.0001 for AML, OAL, CML & ALL). Effect of time period on survival for MDS was not done, as it became formally reportable in 2001. Having >2 primaries was associated with an unfavorable outcome for subsequent AML (HR=1.15; 1.08-1.23; p < 0.0001), MDS (HR=1.13; 1.05-1.22: p=0.001) & CML (HR=1.30; 1.13-1.48: p=0.0002). In multivariable analyses, advancing age was an independent adverse prognostic factor for all secondary leukemias & MDS, both as a continuous variable & when categorized as <60 yrs vs. >60 yrs (p<0.001). Race & gender did not impact survival. Using breast cancer as a referent primary, AML pts had worse outcomes following colorectal (HR=1.31; 1.14-1.5; p=0.0002) or lung (HR=1.46; 1.22-1.74; p< 0.0001) primaries, while MDS pts fared worse with prior lung (HR=1.61; 1.22-2.12; p=0.0007) or Non-Hodgkin lymphoma (HR=1.58; 1.3-1.92: p< 0.0001). Of all 2ndCML cases, those after colorectal cancer had worst survival (HR=1.54; 1.12-2.13; p=0.008). Among SHM pts, MDS pts had better survival than those with AML (HR=0.42; 0.4-0.44: p< 0.0001), as did pts with CML (HR=0.37; 0.35-0.41: p< 0.0001) & ALL (HR=0.64; 0.58-0.70; p< 0.0001). Out OAL had similar outcomes compared to AML (HR=0.99; 0.92-1.05; p=0.66). Pts with CML fared better than MDS (HR=0.47; 0.41-0.54; p< 0.0001) & OAL (HR=0.37; 0.34-0.41: p< 0.0001). Pts with ALL had worse survival than CML (HR=1.8; 1.6-2.03: p< 0.0001) & MDS (HR=1.28; 1.11-1.48: p=0.0005), but better than OAL (HR=0.65; 0.58-0.73: p< 0.0001). (Figure 1) Patients with all SHM, except CML, had worse outcomes compared to those with primary hematologic cancers (Figure 2). Conclusion The prolonged latencies for SHM in this study suggest that they are likely therapy-related. Our findings show that type & number of primary cancers influence survival of subsequent leukemias & MDS. SHM have worse survival compared to those with primary hematologic malignancies except CML where non-separation of survival curves suggest that CML as SHM does not behave like a therapy-related neoplasm. Disclosures Sekeres: TetraLogic: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene Corporation: Membership on an entity's Board of Directors or advisory committees.

Abstract Introduction: Surveillance, Epidemiology, and End Results (SEER) registry captures data on acute leukemias (AL) that morphologically do not conform to well characterized acute leukemic entities in the established French-American-British (FAB) nomenclature. Not much is known about population level outcomes of these rare AL. We performed a comprehensive survival analysis of these rare AL over a forty-year period using the SEER registry. Methods: SEER 18 dataset was queried to identify adult patients (pts > 18 years) diagnosed with Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL) and rare AL from 1973-2012. Rare AL cases were identified using ICD-O-3 morphology codes and included Leukemias, Not Otherwise Specified (NOS) (9800-01, 9860) and myeloid sarcoma (9930). Data on demographics,follow up and survival was abstracted. Univariate and multivariate analysis was performed to identify factors influencing survival of rare AL and survival patterns were compared to AML and ALL. Hazard ratios (HR) with 95% confidence intervals (CIs) are reported. Results: We identified 61,550 AML pts, 13,457 ALL pts, 525 myeloid sarcoma pts and 13,446 pts with leukemia NOS. Median age at diagnosis was 68 years (yrs, range 18-100) for AML, 54 yrs (18-100) for ALL, 65 yrs (18-95) for myeloid sarcoma and 76 yrs (18-100) for leukemia NOS. Gender distribution was similar with females comprising 45.9% of AML, 43% of ALL, 42.3% of myeloid sarcoma and 47.2% of leukemia NOS cases. Over 80% pts in all categories were Caucasian. Median survival was as follows: 0.4 (0-40) yrs for AML; 1.4 (0-39.8) yrs for ALL; 0.7 (0-32.9) yrs for Myeloid Sarcoma; and 0.3 (0-38.9) yrs for leukemia NOS. In univariable analysis, younger age predicted for better survival for both myeloid sarcoma and leukemia NOS (p<0.0001). Improvement in survival over time period was observed for pts with leukemia NOS (p < 0.0001). In multivariable analysis, advancing age was an independent prognostic factor for rare AL, both as a continuous variable and when categorized as older vs. younger pts using age cutoff of 60 yrs. Compared to younger pts, HR for pts > 60 yrs with rare AL was as follows: 2.68 (2.13-3.37; p <0.0001) for myeloid sarcoma; and 2.18 (2.07-2.31; p<0.0001) for leukemia NOS. No difference in survival over time was seen for myeloid sarcoma. Pts with leukemia, NOS diagnosed in yrs 2006-2012 (HR=0.87; 0.82-0.92; p < 0.0001) had better survival compared to the referent years 1973-80. Race and gender did not impact survival. In multivariable analysis, pts with leukemia NOS did worse overall compared to AML (HR=1.13; 1.11-1.53; p<0.0001) and ALL (HR=1.86; 1.81-1.91; p<0.0001). Interestingly, younger pts had a poorer outcome than AML (HR=1.10; 1.04-1.16; p=0.0003), but pts > 60 yrs had a better outcome (HR=0.93; 0.91-0.95; p<0.0001). Both younger (HR=1.33; 1.26-1.41; p<0.0001) and older pts (HR=1.45, 1.40-1.50: p<0.0001) compared unfavorably to ALL (Figure 1). Pts with myeloid sarcoma had a better survival compared to AML pts (HR=0.77; 0.7-0.85; p<0.0001) (Figure 2). This was uniform for pts <60 yrs (HR=0.77; 0.64-0.93; p=0.006) and > 60 yrs (HR= 0.77; 0.69-0.87; p<0.0001). Conclusion: Pts with leukemias NOS have poor outcomes compared to AML and ALL but prognosis has improved in recent years. The most probable explanation is identification of prognostic molecular mutations that has allowed accurate risk-stratification of pts using the WHO classification and in turn better selection of treatment strategies. Several reasons have limited our understanding of these rare AL - small numbers, exclusion from clinical trials and wide variability in treatment options used. Efforts at better molecular characterization of these AL holds the most promise for improving outcomes. Disclosures Sekeres: Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; TetraLogic: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees.