An Interim Analysis of the Turkish Myeloma Registry Among the Patients Who Have Received up to Two Lines of Therapy

Abstract Introduction: To investigate the demographics and treatment details of the myeloma patients who were diagnosed and followed up in Turkey and received up to two lines of therapy. Methods: Patients who were recorded on the database of Turkish Myeloma Registry project were included in this study if they had only received one or two lines of therapy. Demographics, patient, and disease related parameters both at the time of diagnosis and at the follow up and treatment outcomes were presented. Results: A total of 532 patients were included in the study, and 44% of the patients were female. Median age at the time of diagnosis was 63 (30-106). 47.7% of the patients were diagnosed with IgG myeloma. According to the ISS risk stratification, 20.4% of patients had ISS 1, 34.7% of patients had ISS 2 and remaining 44.9% had ISS 3 disease. Defining high risk disease as harboring one or more of these following cytogenetic abnormalities; del 17p, t(4;14), t(14;16) or t(14;20); 7.1% of the patients were classified as having a high risk disease. Most commonly used frontline therapy approach was bortezomib cyclophosphamide dexamethasone combination (VCD) (76.5%) and followed by bortezomib dexamethasone (VD) (8.8%), and bortezomib lenalidomide and dexamethasone combination (VRd) (7.1%). Overall response rates (a better response than stable disease according to IMWG response assessment criteria) were 87.6% in VCD induced patients; 63.3% in VD induced patients and 92% in VRd induced patients. The PFS obtained by these frontline approaches was 17.8 months in patients who were able to proceed with high dose chemotherapy with ASCT support and 8.4 in patients who were not able to (p<0.01), with an overall PFS of 15.3 months. With regard to the induction approach, PFS was 21.1 months for VRD, 15.3 months for VCD and 7.6 months for VD (p=0.08). Regarding maintenance, 23.6% of patients were maintained by lenalidomide alone, 62.7% of patients were maintained by a combination of lenalidomide and dexamethasone or bortezomib alone (2.7%). PFS after the first line of the treatment was 22.2 months in maintained patients and 12.2 in un-maintained patients (HR: 0.532, p=0.001, CI95% 0.359-0.790). Regarding the second line therapy Rd was the leading option (34.8%) and VRd (17.8%), Carfilzomib based (16.3%), VCD (8.1%) were the followings. Conclusion: As the main concern of this study was to document the demographic features and clinical parameters of a Turkish Myeloma population and to give an idea about the treatment patterns and outcomes in frontline setting and first relapse an overall survival was not calculated. Progression free survival obtained after frontline therapy was relatively shorter than the ones which were presented by other real- world registries. Outcomes of second line therapy will be presented as follow up after 2nd line therapy exceeds a certain threshold. We hope, the results obtained from this study can have a role in the approval and re-imbursement of the current standard of care options. Disclosures No relevant conflicts of interest to declare.

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Splenectomy Is Still a Valid Option For Splenic Marginal Zone Lymphoma

Blood ◽

10.1182/blood.v122.21.5129.5129 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5129-5129

Author(s):

Alessandro Pulsoni ◽

Pasqualina D'Urso ◽

Gianna Maria D'Elia ◽

Giorgia Annechini ◽

Caterina Stefanizzi ◽

...

Keyword(s):

Marginal Zone ◽

Conflicts Of Interest ◽

B Cell Lymphoma ◽

Marginal Zone Lymphoma ◽

Splenic Marginal Zone Lymphoma ◽

Spleen Size ◽

Second Line ◽

Second Line Therapy ◽

Line Therapy

Abstract Introduction Splenic marginal zone lymphoma (SMZL) is an indolent B-cell lymphoma characterized by splenomegaly, frequent moderate lymphocytosis with or without villous morphology and possible involvement of various organs, especially the bone marrow (BM). Diagnosis is classically based on the spleen histology, but it can be made on the BM biopsy, based on the typical intrasinusoidal cell infiltration pattern and immunohistochemistry. Different therapeutic options are available, but to date there are no conclusive comparative data. Patients and methods We retrospectively analyzed 83 consecutive patients with a diagnosis of SMZL observed at our Institution between 1999 and 2013. The diagnosis was based on the BM biopsy in 79 patients; the BM was negative in 4 patients. Diagnosis was histologically confirmed on the spleen in 27 patients who underwent splenectomy. Patients presented a median age of 72.5 years (range 38-84); 43 were males. The median spleen size at diagnosis was 145 mm, ranging from 100 to 300 mm. The majority of patients were stage IV at diagnosis for BM infiltration (95%); B symptoms were present in 4 of them (4.8%). Forty-two patients (50.6%) had a lymphocytosis at diagnosis and 13 (15.6%) presented an IPI score higher than 3. Thirty-five of them (42%) had a MZL BM infiltration superior to 30% of the total bone cellularity. Forty-two patients (50.6%) underwent a watch and wait policy (WW), while 41 (49.4%) were treated within 6 months from diagnosis, mainly because of symptomatic splenomegaly; in these patients, treatment consisted of splenectomy, chemotherapy or chemotherapy plus immunotherapy with Rituximab. The features of patients submitted to WW with respect to patients treated at diagnosis were comparable for the various parameters mentioned above, except for spleen size (higher in patients treated at presentation) and lymphocyte count (higher in patients who were observed). After a median follow-up of 64 months, the overall median survival was 96%. Among the 42 WW patients, 18 (42.8%) are still untreated after a median follow-up of 57.5 months, while 24 (57.2%) have required therapy; the median treatment-free interval in these patients was 25.5 months. Concerning the 41 patients who underwent treatment at diagnosis, after a median follow-up of 50 months, 13 (31.7%) have required a subsequent second-line treatment. The interval between first-line approach and re-treatment in patients treated at diagnosis was 30 months. Overall, 27 patients were treated with splenectomy only (either at diagnosis or after a WW period): only 6 of them (22%) had a subsequent progression after a median latency of 42 months; 26 were treated with chemotherapy alone (alkylating agents in the majority of them, combination therapy in a minority): 15 of them (60%) had a subsequent relapse or progression after a median of 9 months; 12 patients received a Rituximab-containing regimen: of these, only 2 (16%) have so far required a second-line therapy after 10 and 26 months respectively. Conclusions The WW policy is a valid option for asymptomatic patients: in these patients, after 4.5 years from diagnosis more than 40% is still untreated. In patients requiring treatment, splenectomy alone is followed in the majority of patients by a long period of good disease control: only 22% required a second-line therapy after 3.5 years. The addiction of Rituximab to chemotherapy seems to reduce the probability of relapse and to prolong the response duration. However, these preliminary data need to be confirmed by larger studies. Disclosures: No relevant conflicts of interest to declare.

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Outcomes in patients (pts) with advanced renal cell carcinoma (aRCC) who discontinued (DC) first-line nivolumab + ipilimumab (N+I) or sunitinib (S) due to treatment-related adverse events (TRAEs) in CheckMate 214.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.7_suppl.581 ◽

2019 ◽

Vol 37 (7_suppl) ◽

pp. 581-581 ◽

Cited By ~ 7

Author(s):

Nizar M. Tannir ◽

Robert J. Motzer ◽

Elizabeth R. Plimack ◽

David F. McDermott ◽

Philippe Barthelemy ◽

...

Keyword(s):

Risk Groups ◽

High Dose ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Line Therapy ◽

Post Hoc ◽

Study Dose ◽

Clinical Trial Information

581 Background: The phase 3 CheckMate 214 trial demonstrated superior efficacy for N+I vs S in aRCC, although more patients discontinued N+I compared with S due to TRAEs. This is a post hoc analysis of outcomes in pts who DC N+I or S due to TRAEs. Methods: Untreated pts with clear cell aRCC were randomized 1:1 to N 3 mg/kg + I 1 mg/kg Q3Wx4 (induction) and then N 3 mg/kg Q3W (maintenance), or S 50 mg daily for 4 wk on, 2 wk off (6-wk cycles). This analysis includes all pts who DC due to TRAEs reported during extended follow-up (≤100 d after last study dose). Results: Of 550 N+I randomized pts, 135 (25%) DC due to TRAEs, most commonly increased ALT, diarrhea, and increased AST (all 3%); 64 (12%) of 535 S randomized pts DC due to TRAEs, most commonly increased ALT, diarrhea, and pancreatitis (all 1%). In N+I pts who DC due to TRAEs, 47% DC during N+I induction, 7% completed induction but no N maintenance, and 46% completed induction and received N maintenance (median [range] 8 [1–47] doses). At 30-mo minimum follow-up, ORR per investigator, CR rate, and 24-mo OS rate were higher in pts who DC N+I vs S due to TRAEs. Outcomes in pts who DC S due to TRAEs were similar to those in all S ITT pts and worse than in N+I pts who DC due to TRAEs (Table). At 24 mo, 42% of pts who DC N+I due to TRAEs were alive and free from second-line therapy. Consistent outcomes were seen in pts who DC N+I due to TRAEs across IMDC risk groups (data to be presented). Pts who DC N+I due to TRAEs experienced more immune-related select TRAEs and received more high-dose steroids (≥40 mg prednisone daily or equiv.), but times to onset and resolution and resolution rates of select TRAEs were similar vs all treated N+I pts. Conclusions: Discontinuation of first-line N+I due to TRAEs did not result in impaired outcomes, and a high proportion of pts remain alive and free from second-line therapy. Clinical trial information: NCT02231749. [Table: see text]

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Life after Fludarabine, Cyclophosphamide, & Rituximab (FCR) - the Clinical Outcome of Patients with Chronic Lymphocytic Leukemia Who Receive Salvage Treatment after Frontline FCR.

Blood ◽

10.1182/blood.v112.11.2090.2090 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2090-2090 ◽

Cited By ~ 4

Author(s):

Constantine S. Tam ◽

William G. Wierda ◽

Susan O’Brien ◽

Susan Lerner ◽

Issa F Khouri ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Stem Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Salvage Treatment ◽

Refractory Disease ◽

Second Line ◽

Second Line Therapy ◽

Line Therapy

Abstract The FCR regimen is the most active treatment program in CLL, with 72% of frontline patients achieving a complete remission (CR) lasting a median of 7 years. However, most patients are not cured and will eventually relapse with CLL. In order to evaluate how these patients should be subsequently managed, we analyzed our institutional experience with 300 patients treated with frontline FCR (Blood 112:975). After a median follow-up of 6 years, 116 patients (39%) had failed FCR therapy with 13 primary refractory disease and 103 relapses from partial remission (PR), nodular PR (nPR) or CR. Compared with patients in ongoing remission, relapsed/refractory patients had more adverse baseline characteristics including a greater proportion with performance status ≥ 1 (71% vs 53% p=0.002), elevated β2m (54% vs 36% p=0.002), white cell count ≥ 150 x 10^9/L (25% vs 12% p=0.003), unmutated IgVH (81% vs 44% p<0.001) and ZAP-70 positivity (78% vs 49% p<0.001). The aim of the current analysis was to determine the duration of survival (OS) following second-line therapy in 97 patients who had completed salvage treatment. The median follow-up was 32 (range 3 – 69) months, and the median OS (mOS) was 32 months. Characteristics associated with favorable OS were: (1) previous best response to FCR of nPR/CR lasting ≥ 18 months (mOS 47 months, vs 13 months for primary refractory disease, PR or nPR/CR lasting <18 months p=0.002); (2) β2m < 3.0 mg/L (mOS not reached, vs 17 months p=0.0003) and (3) platelets ≥ 100x10^9/L (mOS 47 months, vs 15 months p=0.004). Poor risk cytogenetic abnormalities were common at FCR failure: among 38 assessable patients, 7 (18%) had 17p- and 18 (47%) had 11q- by conventional karyotyping and/or FISH. Although patients with 17p- or 11q- had an inferior survival, this survival disadvantage was confined entirely to those who also had an elevated β2m ≥ 3.0 mg/L. Surprisingly, patients relapsing after durable FCR remissions (≥ 5 years) and patients with slowly progressive relapse (time to salvage ≥ 12 months after FCR failure) had similar OS as their more adverse counterparts (p=0.76 and 0.86 respectively). A prognostic model comprising β2m and platelet count effectively divided patients into low, intermediate and high risk categories with mOS of >45, 32 and 13 months respectively (p<0.0001). Patients received treatment chosen at the discretion of individual treating physicians and the CR rate of second-line therapy were: FCR (n=30), 17%; rituximab (n=25), 4%; alemtuzumab ± rituximab (n=16), 31%; FCR & alemtuzumab (CFAR, n=9), 56%; lymphoma-type chemotherapy (n=5), 0%; other treatment (n=12), 0%. The CR rate for CFAR was significantly higher than that of FCR (p=0.03), although the median remission duration (30 vs 20 months) and OS (44 vs 32 months) were similar (p=0.87 and 0.51 respectively). None of the regimens showed a significant survival benefit. Allogeneic stem cell transplantation (SCT) was performed in 27 (28%) patients at a median of 15 months after first salvage. Patients receiving SCT had a significantly superior OS than those who did not undergo SCT (not reached vs 30 months, p=0.03). Of the 14 patients surviving for more than four years, 11 (79%) had undergone a SCT. Patients who fail FCR therapy had high risk disease features including elevated β2m, unmutated IgVH and ZAP-70 positivity, and most had adverse cytogenetic findings at relapse. Results of salvage therapy in this group were poor with a median survival of less than three years. The majority of long-term survivors had received allogeneic stem cell transplantation.

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Fludarabine, Cyclophosphamide and Rituximab (FCR) Related Prolonged Cytopenia Is Frequent and Adverse Factor Affecting Survival of Patients with Chronic Lymphocytic Leukemia (CLL)

Blood ◽

10.1182/blood.v120.21.1790.1790 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1790-1790

Author(s):

Petra Obrtlikova ◽

Anna Jonasova ◽

Magda Siskova ◽

Eduard Cmunt ◽

Adela Berkova ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Lymphocytic Leukemia ◽

High Dose ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy ◽

Significant Difference

Abstract Abstract 1790 Background: The immunochemotherapy regimen composed of fludarabine, cyclophosphamide and rituximab (FCR) has emerged as highly effective frontline or second line therapy for chronic lymphocytic leukemia (CLL). This regimen may be however associated with prolonged cytopenia and the risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Aims and methods: In our retrospective single center analysis, we evaluated the efficacy and the toxicity of FC or FCR regimen in unselected population of CLL patients with treatment indication. The overall survival (OS) and progression free survival (PFS) was calculated for all patients as intent to treat analysis. The prolonged cytopenia was defined as cytopenia (grade 2–4 according to CTCAE v.4 ) developing during of after the last cycle of FC/FCR and persisting two or more months. Cytopenia was evaluated in patients with follow-up at least 6 months after this treatment. Patients were excluded from analysis of cytopenia if they underwent immediate other treatment (antibody maintenance, high dose therapy with autologous stem cell transplantation (ASCT) consolidation, or they received other therapy due to unsatisfactory response to FCR). Patients with missing laboratory data after FC(R) were also excluded. Kaplan Maier curves for PFS and OS were calculated and log rank test was used for survival comparison. Results: Altogether, 252 patients started the treatment with FC or FCR in the years 2000–2012 at our institution. There were 86 (34%) women and 166 (66%) men with a median age of 62 years (31–87) at the time of FC(R) therapy. 52 (21%) pts received FC regimen, including 40 pts treated in first line therapy and 12 pts in second line therapy. FCR therapy was administered in 200 pts (79%): 153 pts received FCR as first line therapy, 38 pts as second line therapy and 8 pts as third or fouth line therapy. The median number of FC cycles was 5 (1–8) with or without R. The estimated OS for the first line therapy was 87,5% in FCR group vs 80% at 3y in FC group (p ns) (Hallek,CLL8: 87% vs 83%) and PFS was 70% in FCR group vs 50% in FC group (p=0,004) with the median of follow-up 45 months. Altogether 184 pts fulfill the criteria for cytopenia analysis. The most frequent immediate subsequent therapy considered as exclusion for this analysis was ASCT consolidation (n 20). Out of 184 pts, 146 recieved FC(R) as 1st line treatment and 38 subsequent therapy. The prolonged cytopenia was observed in 54 pts (29%), 42 (29%) in 1st line group and 12 (32%) in subsequent line group. Median duration of cytopenia was 8 m (2–65), 29 out of 54 patients have had persistent cytopenia at the time of last follow up. The cumulative probability to develop cytopenia was 30.3% at 2y among all pts and 29.7% among first line FCR treated pts. There was no significant difference between FC and FCR treated pts. Eleven pts developed MDS/AML, 7 cases were observed in the followed group of 184 pts (with probability 6.1% at 6y), in all cases the cytopenia preceded the MDS onset, 6y probability to develop MDS was 25.2% for patients who develop prolonged cytopenia after FC(R). Moreover 2 MDS and 1 AML were observed among 20 pts treated with ASCT (6y probability 5.6%, 8y probability 22.5%). The OS probability from 1stcycle of FC(R) was significantly better for pts without cytopenia (75.5% vs 57.5% at 5y, p<0.005), nonsigificant trend was observed if only first line FCR pts were analyzed (88% vs 85%). The median survival for the MDS pts from the time of MDS dg was 6 months only. Conclusions: Although the FCR is the best available standard treatment option for CLL pts, it is associated with prolonged cytopenia in 30% of cases. These patients with prolonged cytopenia afte FC(R) have considerably high probability (25.2%) to develop MDS and they have worse OS compared to pts without cytopenia. Disclosures: No relevant conflicts of interest to declare.

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The Outcome of Different Types of Second-Line Therapy in Multiple Myeloma Patients Relapsing After Uniform Front-Line Treatment with High-Dose Melphalan and Autologous Stem Cell Transplantation.

Blood ◽

10.1182/blood.v114.22.2892.2892 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2892-2892

Author(s):

Claudia Crippa ◽

Samantha Ferrari ◽

Monica Drera ◽

Marinella Calarco ◽

Antonio Regazzoli ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

High Dose ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Line Therapy ◽

High Dose Melphalan

Abstract Abstract 2892 Poster Board II-868 Background and aim. While multiple myeloma (MM) still remains largely incurable, therapeutic options for patients with MM are expanding. However the best way to use the different effective regimens, either in combination or in sequence, during the course of MM in the single patient is still unknown. Data from controlled studies rarely report the treatments received before and after the enrollment of patients in the clinical trial, which may significantly impact on response and survival. As an example, the best treatment for patients relapsing after first-line high-dose melphalan (HD-Mel) and autologous stem cell transplantation (ASCT) is not standardized. To this end we have retrospectively analyzed an uniform cohort of such patients treated at our Institution, comparing their outcome according to the type of second-line and further consolidation treatment received. Patients and methods. In 156 patients affected by MM and treated between 1997 and 2008 with HD-Mel and ASCT as first line therapy, relapse has occurred in 92 (59%). Females were 39 (42%), males 53 (58%), median age was 60 (range 34-75). As induction therapy before ASCT, 89 (97%) had received VAD regimen, and only 3 (3%) thalidomide/bortezomib-based regimen. Sixty-one patients (66%) had received a single ASCT and 31 a double ASCT (34%). A second-line therapy was given to 87/92 patients. They were subdivided in 3 subgroups according to the type of second-line treatment received: 1) thalidomide-based regimens (THAL) were given to 55 pts (63%) followed by a consolidation ASCT in 13 (24%) 2) bortezomib-based regimens (BORT) were used in 13 (15%) and subsequent ASCT in 3 of them (23%) 3) chemotherapy and/or steroids (CHEMO) were used in 19 (22%) followed by ASCT in 15 (79%). Median follow-up from diagnosis was 57 (13-145) in THAL, 39 (17-140) in BORT and 59 months (25-113) in CHEMO respectively. The baseline characteristics, including age, of the three subgroups were similar as well as the CR/VGPR and ORR rates obtained after first-line treatment (THAL 47% and 87%; BORT 69% and 100%; CHEMO 53% and 100%, respectively). The subgroups also did not differ in median duration of first response, which ranged from 13 to 15 months and median time to second treatment, which was 26 months in all subgroups. The proportion of patients receiving a double ASCT were significantly higher in BORT (69%) compared to THAL (34%) (P=0.03) and CHEMO (5%) (p=0.002), and in THAL (34%) compared to CHEMO (5%) (p=0.015). Results. After second line therapy the ORR (CR+VGPR+ PR) of the three subgroups was: THAL 60%, BORT 77% and CHEMO 58%. (p=NS). The second CR/VGPR rate was non significantly higher after BORT (46%) than after THAL (25%) or CHEMO (21%) (p=0.17). Moreover, when considering patients not undergoing second-line consolidation ASCT, the ORR was significantly better in THAL and BORT subgroups compared to CHEMO (50%, 70% and 0%, respectively p=0.03). After a median follow-up from second-line treatment of 28 months (range 1-99), the 2-y PFS was 38% after THAL (median 18 months), 34% after BORT (median 16 months) and 17% after CHEMO (median 12 months) (p=NS). The 2-y OS was 78% (median 49 months), 70% (median not reached), and 70% (median 33 month) after THAL, BORT and CHEMO, respectively (p=NS). However when considering patients not undergoing second-line consolidation ASCT, the 2-y OS was significantly better after THAL and BORT than after CHEMO (p=0.024). Conclusion. In spite of having frequently received a first-line double ASCT, BORT patients seemed to achieve responses of better quality. However, in patients relapsing after first-line HD-Mel and ASCT, the choice of THAL, BORT or CHEMO-based regimens as second-line therapy did not seem to impact on overall response rates and survival, provided that patients treated with CHEMO could be consolidated with a second ASCT. Hence newer drugs may be reserved for those patients not fit for ASCT, preserving them for effective third-line treatment in the other patients. Disclosures: No relevant conflicts of interest to declare.

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Effects of multiple courses of oral gefitinib, topotecan, and cyclophosphamide in poor risk neuroblastoma

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.20009 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 20009-20009

Author(s):

A. Donfrancesco ◽

M. De Ioris ◽

A. Jenkner ◽

I. Ilari ◽

L. De Sio ◽

...

Keyword(s):

Cytotoxic Drugs ◽

Fixed Dose ◽

High Dose ◽

Second Line ◽

Second Line Therapy ◽

Primary Tumors ◽

Line Therapy ◽

Heavily Pretreated

20009 Background: Gefitinib (G) has shown potent inhibitory activity on neuroblastoma (NB) cell proliferation in in vitro models. Experimental data have also reported that the addition of G to cytotoxic drugs can increase in vitro and in vivo antitumor activity in several tumor models, but if this will translate in significant clinical benefits, with respect to survival, is still unclear. We evaluated the feasibility of administering an oral regimen including G combined with topotecan (TPT) and cyclophosphamide (CPA) in heavily pretreated pts with relapsed/resistant metastatic NB. Methods: Patients received oral CPA (50 mg/m2/day) followed by TPT (0.8 mg/m2/day) plus G (at the fixed dose of 250 mg/day) for 14 consecutive days in an outpatient setting. Courses were repeated every 28 days until progression, and response was evaluated every second course. Expression of EGFR mRNA in primary tumors was assessed by real-time RT-PCR. Results: Six pts (1M/5F), median age 5.4 years (range 4.1–8.2), were enrolled between October 2004 and October 2006. All pts were relapsed after high-dose chemotherapy and hemopoietic rescue with PBSCs. At the time of inclusion, 3 pts were in PR after 8 courses of second-line therapy, whilst 2 pts had achieved SD after 1 and 8 courses of second-line therapy, resp; 1 pt had PD right after PBSC rescue. Significant levels of EGFR mRNA were detected in 4/6 tumors. A median of 7.5 courses (range 1–24) per pt were administered. In 4 pts, the dose of TPT and CPA was reduced by 25% after the first course. After a median follow-up of 12 months (range 1–26), 1 pt is DOD at 15 months since the inclusion and 5 pts are alive, 1 in VGPR (26+ months) and 5 with SD (26+, 1+, 4+, 9+ and 18+ months). Median PFS is 7.5 months (range 1–26). Neutropenia grade 4 was observed in 4/6 pts; rash grade 2 in 2 pts, and hepatic (LFT increase) grade 3 toxicity in 1. Conclusions: The regimen was feasible and well tolerated in this series of heavily pretreated pts. PFS is encouraging, but deserves further evaluation and longer follow-up. Additional molecular studies are ongoing aimed at identifying the subset of NB pts most likely to benefit from the synergy between G and cytotoxic drugs observed in preclinical models. No significant financial relationships to disclose.

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Relapse After Early-Stage, Favorable Hodgkin Lymphoma: Disease Characteristics and Outcomes With Conventional or High-Dose Chemotherapy

Journal of Clinical Oncology ◽

10.1200/jco.20.00947 ◽

2021 ◽

Vol 39 (2) ◽

pp. 107-115

Author(s):

Paul J. Bröckelmann ◽

Horst Müller ◽

Teresa Guhl ◽

Karolin Behringer ◽

Michael Fuchs ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Early Stage ◽

High Dose Chemotherapy ◽

Sensitivity Analyses ◽

High Dose ◽

Second Line ◽

Second Line Therapy ◽

Line Therapy ◽

Significant Difference ◽

First Diagnosis

PURPOSE We evaluated disease and treatment characteristics of patients with relapse after risk-adapted first-line treatment of early-stage, favorable, classic Hodgkin lymphoma (ES-HL). We compared second-line therapy with high-dose chemotherapy and autologous stem cell transplantation (ASCT) or conventional chemotherapy (CTx). METHODS We analyzed patients with relapse after ES-HL treated within the German Hodgkin Study Group HD10+HD13 trials. We compared, by Cox proportional hazards regression, progression-free survival (PFS) after relapse (second PFS) treated with either ASCT or CTx and performed sensitivity analyses with overall survival (OS) from relapse and Kaplan-Meier statistics. RESULTS A total of 174 patients’ disease relapsed after treatment in the HD10 (n = 53) and HD13 (n = 121) trials. Relapse mostly occurred > 12 months after first diagnosis, predominantly with stage I-II disease. Of 172 patients with known second-line therapy, 85 received CTx (49%); 70, ASCT (41%); 11, radiotherapy only (6%); and 4, palliative single agent therapies (2%). CTx was predominantly bleomycin, etoposide, doxorubicin cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP [68%]), followed by the combination regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (19%), or other regimens (13%). Patients aged > 60 years at relapse had shorter second PFS (hazard ratio [HR], 3.0; P = .0029) and were mostly treated with CTx (n = 33 of 49; 67%) and rarely with ASCT (n = 8; 16%). After adjustment for age and a disadvantage of ASCT after the more historic HD10 trial, we did not observe a significant difference in the efficacy of CTx versus ASCT for second PFS (HR, 0.7; 95% CI, 0.3 to 1.6; P = .39). In patients in the HD13 trial who were aged ≤ 60 years, the 2-year, second PFS rate was 94.0% with CTx (95% CI, 85.7% to 100%) versus 83.3% with ASCT (95% CI, 71.8% to 94.8%). Additional sensitivity analyses including OS confirmed these observations. CONCLUSION After contemporary treatment of ES-HL, relapse mostly occurred > 12 months after first diagnosis. Polychemotherapy regimens such as BEACOPP are frequently administered and may constitute a reasonable treatment option for selected patients with relapse after ES-HL.

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Characteristics, treatment patterns, and economic burden of patients with metastatic cervical cancer receiving systemic anticancer therapy.

Journal of Clinical Oncology ◽

10.1200/jco.2020.39.28_suppl.51 ◽

2021 ◽

Vol 39 (28_suppl) ◽

pp. 51-51

Author(s):

Xiaoyun Pan ◽

Lincy S. Lal ◽

John White ◽

Seyed Hamidreza Mahmoudpour ◽

Christian Valencia

Keyword(s):

Cervical Cancer ◽

Economic Burden ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Duration Of Treatment ◽

Second Line Therapy ◽

Treatment Regimens ◽

Line Therapy

51 Background: In 2021, 14,480 patients are estimated to be diagnosed with cervical cancer in the US; 16% of patients are expected to have metastatic disease for whom the 5-year survival rate is 17.6% per SEER estimates. Patients with metastatic cervical cancer (mCC) are treated mainly with systemic therapy. This study aims to describe the clinical characteristics, demographics, treatment patterns, and economic burden of patients with mCC receiving systemic therapy. Methods: Eligible women had been diagnosed with cervical cancer, as evidenced by >2 outpatient or >1 inpatient claim in the Optum Research Database from January 2014 through January 2020. Patients were included if they had metastasis within 6 months before or after cervical cancer diagnosis, with evidence of systemic treatment on or after the latter of a claim date for cervical cancer disease or metastatic disease. The index date was the first-line treatment initiation date. Patients were required to have ≥6 months of pre-index continuous enrollment. The top 3 treatment regimens and median treatment duration by line of therapy were described. All-cause per-patient-per-month (PPPM) costs (2019 US dollars), including plan and patient paid amounts, were reported for full follow-up period from first-line and second-line therapy initiation. Results: The study sample consisted of 778 patients (mean age, 59 years; commercial, 58%; Medicare Advantage, 42%). The mean (median) follow-up period was 14 (9) months. Top baseline comorbidities were diseases of the urinary system (71%) and diseases of the female genital organs (70%), and the median Charlson comorbidity index was 7. In the first line, 80% of patients received platinum-based therapy and 23% received bevacizumab (bev). Of 778 patients, only 294 (38%) received second-line therapy, with 34% receiving bev. Top first-line treatment regimens were carboplatin + paclitaxel (27%), cisplatin (21%), and bev + carboplatin + paclitaxel (10%); the median (95% CI) duration of treatment was 3.4 (3.1-3.7) months. Top second-line treatment regimens were bev + carboplatin + paclitaxel (13%), carboplatin + paclitaxel (11%), and pembrolizumab (6%); the median duration of treatment was 3.8 (3.1-4.2) months. Mean all-cause total PPPM costs were $19,519 from first-line and $22,660 second-line therapy initiation (table). Conclusions: This study indicates that real-world mCC patients have short treatment durations and significant economic burden with first-line and second-line therapy. Novel therapies associated with greater clinical benefits in patients with mCC may provide economic benefit.[Table: see text]

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