INTRODUCTION: The typical presentation of patients with low grade lymphoma consists of disseminated lymphadenopathy, absence of constitutional symptoms, normal LDH, low Ki-67 and PET scan with low SUVs (i.e. <14). We have identified a subset of atypical cases who present with one or more clinically aggressive features. We have named these cases clinically discordant indolent histologies (CDIH). The goal of this study is to identify these cases with CDIH in order to determine if their prognosis and clinical behavior are different from those with the typical low grade NHL presentation. METHODS: We defined CDIH as any follicular grade 1-2, grade 3-A or small lymphocytic lymphoma (SLL) who meet at least one or more of the following conditions: constitutional symptoms, unexplained LDH elevation, PET SUV >14, Ki67 >30%, unusual areas of involvement for indolent NHL (bone, pleura, CNS, soft tissue, lung), necrotic areas seen in CT scan or discrete space occupying lesions in liver or spleen. We analyzed their failure free survival (FFS), overall survival (OS), rate of transformation to a high grade histology and correlation with FLIPI-2 prognostic score. RESULTS: A total of 97 cases (86 follicular, 11 SLL) with a median follow up of 56 months were identified from our data base. Of these 97 cases, 46 met the criteria for CDIH. Figure 1 shows the FFS of cases with CDIH as contrasted with 51 without CDIH. As is evident from Figure 1, those with CDIH not only had a higher relapse rate but also showed a trend for earlier relapses (within 3 years), reminiscent of high grade NHLs. Figure 2 depicts the OS of CDIH cases which is significantly inferior. We also analyzed the risk of transformation. The rate of transformation of CDIH was 5/46 (11%) in contrast to 0/51 with non CDIH (p=.02). All episodes of transformation occurred early, between 6 to 35 months from diagnosis. In order to determine if there was an underlying lymphoma of high grade histology at diagnosis, 8 cases with CDIH underwent a second biopsy of a site suspected of harboring an aggressive NHL because of findings such as SUV of ≥14. None of the 8 cases showed evidence of a high grade NHL in the second biopsy. In nearly all (94/97=97%) treatment included rituximab in combination with chemo and 80% of these were given maintenance. Management consisted of: Treatment A (n=55)-non-doxorubicin regimens, mostly fludara or bendamustine based; Treatment B (n=19)-R-CHOP; Treatment C (n=23)-R-CHOP x 6 followed by fludara based regimen (FND) x 4. The latter was used primarily for CDIH. Of the 46 cases of CDIH, 31 were treated with a doxorubicin-rituximab combination (either Treatment B or C). Their OS at 8 years was 98 % vs 62% for those who received a non- doxorubicin regimen (Treatment A), p=0.014. Of 40 cases without CDIH who received Treatment A, only 1 has relapsed. FLIPI-2 prognostic score correlated poorly with CDIH: of 23 with high risk score, 12 had CDIH and of 7 with low risk, 3 were CDIH. CONCLUSIONS: 1-Cases with CDIH have less favorable OS, FFS, and higher rate of transformation to a higher grade histology. 2-In spite of the fact that CDIH histologically is identical to an indolent NHL, it functionally behaves as an aggressive NHL with frequent early relapses. 3-FLIPI-2 prognostic score correlates poorly with CDIH. This is not surprising since FLIPI-2 score doesn't include B symptoms and LDH. 4-Confirmatory biopsies to rule out co-existing high grade NHL at diagnosis are not useful or recommended. 5-Those without CDIH do very well when treated with a non-doxorubicin regimen such as a fludarabine-rituximab containing combination while CDIH cases appear to fare better when treated with a doxorubicin-rituximab containing regimen. These conclusions have to be interpreted in light of the retrospective nature of the study. Disclosures No relevant conflicts of interest to declare.
Background: Achieving a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) has been associated with improved disease free survival (DFS) and overall survival (OS). The Residual Cancer Burden Score (RCB) method is a useful tool that predicts DFS and OS after NAC. We present the results of pts with either triple negative or HER2 positive breast cancer treated with a novel NAC. Methods: 34 pts with localized breast cancer >1 cm with HER2+ (N = 19) or triple negative breast cancer (TNBC) (N = 15) were treated with this novel regimen consisting first of TEC (docetaxel 75 mg/m2, epirubicin 80 mg/m2, and cyclophosphamide 500 mg/m2) + PEG Filgrastim x 4 cycles. Following the 4th course, TNBC patients received 4 additional TEC cycles if they achieved CR by MRI, or were switched to a non cross-resistant regimen (vinorelbine, bevacizumab, capecitabine) if they had < CR. HER2+ pts received TEC x4 followed by docetaxel + trastuzumab x 4. RCB score was used to measure pathologic response. Pretreament PET scan was done and repeated after course 1 in order to correlate with RCB. Results: Median age was 56 (58 for Her2+ and 49 for TNBC). RCB = 0 (pCR) was achieved in 76%, while only 1 responded poorly (RCB = 3). There was no significant difference in the pCR rate between Her2+ and TNBC patients (74% vs 80% respectively), but there was a difference in the rate of pCR without DCIS and invasive cancer between these two (see table, p = 0.034). Pts with SUV drop > 5% after 1st TEC had 84% pCR while none with < 5% achieved pCR (p = 0.001). Comparison of our results with other NAC regimens reported in the literature is summarized in the table below: ProtocolpCR (no invasive)pCR(no invasive and no DCIS)RCB 0-1Auxilio Cancer Center HER2+/TNBC74%/80%37%/73%79%/80%I-Spy trial 1 HER2+/TNBC45%/35%N/A61%/40%GeparQuinto HER2+/TNBCN/A45%/38.4%N/ANSABP B-40 TNBC51%N/AN/ANeoAltto HER2+47%N/AN/ANeoSphere HER2+39%N/AN/AMDACC FEC+trastuzumab HER2+60%N/AN/A Conclusions: This novel chemotherapy approach results in a high pCR rate and RCB 0-1, which have been associated with improved clinical outcomes. Early PET can predict pCR. Although sample size is modest, results are encouraging and deserve further evaluation. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-17.
7556 Background: Currently there is no optimal salvage regimen for relapsed/refractory NHL (R/R NHL). Prognosis of pts who fail to achieve CR to salvage therapy is dismal. We sought to improve the CR rate by adding Lenalidomide (L) to GROC (ASCO #8530, 2008). Methods: Primary endpoint was rate of conversion to CR after switch to L for pts whose best response to GROC was <CR. Secondary endpoint was progression free survival (PFS) of all pts as well as those who achieve <CR on chemotherapy and were crossed over to L.Pts who failed to achieve at least PR after GROC x2 and those who didn’t achieve CR after GROC x6, were crossed over to L 25 mg x 3 weeks q 28 days. CRs were maintained on L x 2 yrs. Results: 34 pts were enrolled of which 32 are evaluable. Median age: 61 and 56% males. Histologies included DLBCL (81%), PTCL (9%), follicular grade 3-B (9%). Stage was III-IV in 75% and median IPI=2. Best overall response rate (ORR) at any point during treatment= 19/32 (59%) and CR 13/32 (41%). ORR before crossover to L=13/32 (41%) and CR= 8/32 (25%). There were 24 who failed to achieve CR on GROC (19 who didn’t respond at all and 5 whose maximum response was PR). Of these, 21 crossed over to L and 7 (33%) responded (CR in 5, PR in 2). The fact that 5 pts attained a CR to L thus improving the CR rate from 25% to 41% after exhibiting refractoriness to GROC is noteworthy. Of the 7 responders to L, all are alive and only 1 relapsed. At 2 yrs., overall survival (OS) was 48% and PFS 35%. This compares favorably with our previous GROC study without L in which 2 yr. OS= 33% and PFS 29%. In total, 11 pts were eligible for ASCT after chemo plus L and 8 were transplanted (3 refused). Of these eight, 6 remain in CR at 11, 18, 21, 22, 52, 74 mos. At 2 yrs, PFS for transplanted pts is 73% and for those whose response to GROC before crossover to L was <CR, it is 27 mos. Toxic events included 2 neutropenic fevers, 1 MDS (34 mos. after ASCT) and 1 AML (11 mos. after ASCT). Both of these remain continuously in CR after allo SCT. Conclusions: 2 yrOS=48% and PFS=35% with GROC-Rev are the best observed with any salvage regimen we have tested. L is active as a single agent in 29% of cases whose best response to GROC was <CR. A larger study is desirable to confirm these data. Clinical trial information: NCT01307592.
e18547 Background: Prognostic factors in NHL have been well studied in the pre-rituximab era. More recently, tumor infiltrating macrophages were found to confer an adverse prognosis. Porrata et al. at Mayo Clinic have described the ALC, AMC, and ALC/AMC ratio as important prognostic factors. We have evaluated pts with aNHL treated in the rituximab era to identify prognostic factors Methods: From January 2006 and April 2011, 89 pts with aNHL treated at our center were accrued. Initial treatment was R-CHOP based. 59 were entered on R-CHOP + GM-CSF protocol and the remainder were identified from our database. Results: Median age was 59 (25-89), 44% were male; histologies included DLBCL (n=75), high grade follicular lymphoma (n=11), and other (n=5). Median follow up = 27 mo. 3 year FFS and OS for the entire group: 78% and 83% respectively. On univariate analysis, FFS was superior for low IPI (0-2, p=0.01), normal B2 microglobulin (p=0.008), females (p=0.04), ALC > 865 (p=0.001), ALC/AMC ratio of >1.43 (p=0.02) but contrary to Porrata’s findings, there was no difference by AMC. In pts with low IPI, there was a significant difference in FFS and OS for those with an ALC >865 (93% vs 56%, p=0.0008;96% vs 60%, p=0.0004). In females ALC had no prognostic value, but males with low ALC had a significantly worse FFS and OS (85 vs 34%, p=0.007; 91% vs 53%, p=0.006). Females with high AMC had superior FFS (p=.02) but the opposite trend was seen in males. On multivariate analysis, gender, B2-microglobulin, and combined IPI with ALC/AMC ratio >1.43 remained as independent prognostic factors with gender being the most significant factor in the model. Conclusions: Prior to Rituximab, gender was not prognostic. Our findings suggest that: 1- favorable impact of Rituximab occurs mostly in females; this could be related to their immune system. 2- Both ALC and ALC/AMC ratio have prognostic significance, and can identify patients with favorable IPI who have poor outcome. This effect is particularly striking for males. To the best of our knowledge this is the first study to find an interaction between gender and ALC, and ALC/AMC as well as a divergent effect of gender and AMC on prognosis
e19510 Background: MZL is an indolent NHL composed of 3 subtypes: extranodal (MALT), splenic marginal zone (SMZL) and nodal marginal zone (NML). While MALT usually presents with early stage, the others frequently present with advanced disease. Early stage MALT is usually treated with XRT or antibiotics with ~85-90% failure free survival (FFS) and overall survival (OS), while for SMZL watch and wait or splenectomy (Spl) have been the mainstay of therapy. Spl leads to improvement but rarely to CR. 5 yr FFS and OS with Spl have been 45% and 80%. At 10 yrs FFS and OS are 22% and 62%. NML is usually managed with watch and wait. The 5 yr FFS and OS for NML have been 30% and 60%. Watch and wait and Spl are used in part because advanced MZL is considered incurable. Rituximab (R) as well fludarabine (F) are active in this disorder but traditionally are given after relapse. Methods: Instead of watch and wait or Spl, we have used upfront chemo with curative intent for SMZL and NML as well as for advanced MALT. For early stage MALT we used either XRT alone or antibiotics. We hereby report on 44 pts with MZL of which 31 were MALT, 9 SMZL, 4 NMZL. For the purpose of analysis we divided the pts in 2 groups. Group 1 consists of 22 early stage MALT who were all treated with either XRT (N=17) or antibiotics +/- surgery (N=5). Group 2 consists of 22 cases who were treated with chemo alone. This group is made up of 9 MALT (4 advanced stage, 3 early stage but with transformation, 2 early stage but in whom XRT was contraindicated), 9 advanced stage SMZL, 4 NML. Chemo for group 2 consisted of F, mitoxantrone, dexamethasone, rituximab (FND-R) (N=14) or R-CHOP (N=8). Maintenance R was used in 70% of group 2. Results: Of the whole group, 100% were CR and only 2 relapsed at 70 and 75 months; both relapses were stage I MALT and had received XRT only. Both were salvaged with FND-R and remain NED 27 and 39 months from relapse. At 10 yrs, FFS was 80% and OS=100%. None of the 22 in group 2 have relapsed. The long-term toxicity has been acceptable. Conclusions: The excellent FFS and OS using upfront chemotherapy in group 2, suggests that this disorder is curable and our results should be confirmed in a prospective trial. For those with early stage MALT, XRT alone +/- antibiotics and when necessary salvage with FND-R, should be tested.
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