Comparing Eras: Assessing Treatment Trends before and after Ruxolitinib Approval

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3124-3124
Author(s):  
Andrew Kuykendall ◽  
Chetasi Talati ◽  
Najla Al Ali ◽  
Eric Padron ◽  
David Sallman ◽  
...  
Keyword(s):  
Patient Population ◽  
Research Funding ◽  
First Line ◽  
Jak2 Inhibitor ◽  
First Line Therapy ◽  
Line Therapy ◽  
Fda Approval ◽  
Before And After ◽  
Frontline Therapy ◽  
To Receive

Abstract Background: Ruxolitinib is a JAK1/2 inhibitor that gained FDA approval for treatment of intermediate and high-risk myelofibrosis (MF) in 2011. Prior to ruxolitinib, a variety of treatments were used for myelofibrosis, with variable efficacy. Even in the ruxolitinib era, treatment decisions are primarily focused on symptom management, as no treatment, other than allogeneic hematopoietic stem-cell transplant (allo-HSCT) has shown to have a strong disease-modifying effect. Ruxolitinib significantly improves splenomegaly and constitutional symptoms associated with MF. Here, we aim to compare MF treatments before and after ruxolitinib approval to assess treatment patterns and impact on clinical outcomes. We hypothesized that an increased use of ruxolitinib after its FDA-approval would affect those with constitutional symptoms and/or splenomegaly and correlate with decreased use of other treatments aimed at these symptoms. Methods: This was a single institution, retrospective study of all patients with a diagnosis of MF who were seen at our center between 2/2001 and 6/2016. The World Health Organization 2016 definition of primary myelofibrosis (PMF) was used for confirmation of diagnosis. Initial treatment was defined as first treatment after diagnosis of MF. Specific phenotypes were assigned retrospectively based on chart review reflecting the patient's initial complaints which led to diagnosis. Results: We identified 312 eligible patients. This group was divided into two cohorts: those diagnosed prior to the ruxolitinib era (cohort PRE, n = 177) and those diagnosed in the ruxolitinib era (cohort POST, n = 135). Demographics (gender, race, age at diagnosis) and presenting features were comparable between the cohorts. In the PRE cohort, JAK2 inhibitor use occurred in the setting of a clinical trial as well as in patients who were diagnosed prior to ruxolitinib approval, but first received treatment after its approval. In this cohort, 25% of patients received a JAK2 inhibitor, with 36% of these patients receiving it as frontline therapy (see figure 1). This compared to 44% of POST patients who received a JAK-2 inhibitor, with 69% receiving it in the frontline setting. POST patients were, more likely to receive ruxolitinib overall (OR 2.28, p = 0.001) and as first-line therapy (OR 4.49, p < 0.0001). POST patients were less likely to receive an erythropoiesis-stimulating agent (ESA) overall (OR 0.40, p = 0.0003) and as first line therapy (OR 0.51, p = 0.02). Thalidomide was also less commonly used in the POST patients (OR 0.34, P = 0.003). The use of hydroxyurea was similar between cohorts. When stratified based on the presence of constitutional symptoms (CS) and/or splenomegaly (S), patients most commonly received an ESA, JAK-2 inhibitor, or hydroxyurea as frontline therapy (see figure 2). When both CS and S were present, patients more commonly received the latter two options. Patients presenting with CS and S were more likely to receive ruxolitinib as first line therapy in the POST cohort compared to the PRE (OR 5.5, p = 0.0004); however, the use of first line hydroxyurea was not significantly different between the PRE and POST cohorts (p = 0.28). In all, ten separate frontline treatments were used in the symptomatic PRE cohort while only five were utilized in POST patients. In patients presenting without constitutional symptoms or splenomegaly, there was no difference in initial treatment strategy in the PRE and POST cohorts, and ruxolitinib was rarely utilized in this patient population. No difference in overall survival (OS) was noted between the two cohorts. Conclusion:After FDA-approval, ruxolitinib has emerged as the most common first-line treatment option for MF, specifically in patients with constitutional symptoms and splenomegaly, with decreased up-front use of thalidomide, ESAs and hydroxyurea. Patients presenting without constitutional symptoms or splenomegaly were no more likely to received ruxolitinib in the post-approval era, indicating a preference for alternative treatment options in this group. Longer follow up is needed to assess survival impact of frontline ruxolitinib use in our patient population. Disclosures Sweet: Karyopharm: Honoraria, Research Funding; Ariad: Consultancy, Speakers Bureau; Pfizer: Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Incyte Corporation: Research Funding. Komrokji:Novartis: Consultancy, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Lenalidomide Treatment For Lower Risk Non-Deletion 5q Myelodysplastic Syndromes Patients Yields Higher Response Rates When Used Prior To Azanucleosides

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1507-1507
Author(s):  
Rami S Komrokji ◽  
Maria G. Corrales-Yepez ◽  
Najla H Al Ali ◽  
Eric Padron ◽  
Jeffrey E Lancet ◽  
...  
Keyword(s):  
Overall Survival ◽  
Myelodysplastic Syndromes ◽  
Lower Risk ◽  
Research Funding ◽  
Response Rates ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy

Abstract Introduction Lenalidomide (LEN) is the standard of care for treatment of transfusion dependent lower risk myelodysplastic syndromes (MDS) with chromosome 5q deletion (del 5q). In the MDS-002 study, 26% of lower risk transfusion dependent MDS patients became red blood cell transfusion independent after LEN treatment. National Comprehensive Cancer Network (NCCN) clinical guidelines list LEN as a second line treatment alternative for transfusion dependent anemia in lower risk non-del 5q MDS after azanucleosides failure. The response rate to LEN after azanucleosides failure, however, is not known given that the MDS-002 study preceded FDA approval of azanucleosides. To address the best sequence of LEN to optimize response potential in lower risk MDS, we examined the response rates to LEN in non-del 5q lower risk MDS when offered as first line after (erythroid stimulating agents) ESA's or after azacitidine failure. Methods This was a retrospective study conducted using the Moffitt Cancer Center (MCC) MDS database. We identified patients with lower risk MDS who received both LEN and azacitidine as first or second line therapy after erythroid stimulating agents. Lower risk MDS was defined according to the international prognostic scoring system (IPSS) Low or intermediate-1 (int-1) risk groups. The primary endpoint was to compare rates of erythroid hematological improvement (HI-E) between the group of patients who received LEN as first line therapy followed by azacitidine as second line (LEN 1st line group) and those who received LEN as second line therapy after azacitidine (LEN 2nd line group). HI was defined according to international working group criteria (IWG 2006). Chi- square test was used for categorical variables, T-test was used for continuous variables, and Kaplan Meier estimates for overall survival. All analyses were conducted using SPSS statistical software (IBM version 21) Results We identified 63 patients who received both azacitidine and LEN as first and second line where 37 patients were in group 1 (LEN 1st line) and 26 patients were in group 2 (LEN 2nd line). Baseline characteristics between the two groups are summarized in Table-1. There were no statistically significant differences between the 2 groups in terms of mean age at diagnosis, gender, WHO subtype, revised IPSS, or mean blood counts. The majority of patients had refractory cytopenia with multilineage dysplasia (RCMD) and had low risk revised IPSS . The rate of HI-E was 38% (n=14) among LEN 1st line group compared to 12% (n=3) in LEN 2nd line group. (p=0.04). There was no difference in overall survival (OS) among the two groups with a median OS of 104 months and 87 months, respectively, p=0.55. There was no difference in AML transformation rate, 5.4% (n=2) and 11% (n=3) among the two groups, respectively, p=0.33. There were no differences in response rates to azacitidine among the two groups. Among the Len 1st line group response to 2nd line azacitidine was 38% (n=14) compared to 35% (n=9) among those who received azacitidine as first line followed by LEN as 2nd line. (p=0.69). Conclusion LEN yields a higher rate of HI-E in non-del 5q lower risk MDS when used as first line therapy. If validated in a larger cohort, LEN should be considered for 1st line therapy after ESAs rather than after azacitidine failure. Responses to azacitidine were similar among the two groups, indicating no adverse effect of LEN on azacitidine response. Disclosures: Komrokji: Celgene: Research Funding, Speakers Bureau. Off Label Use: use of lenalidomide in non del 5q. Lancet:Celgene: Research Funding. List:Celgene: Research Funding.

Skeletal-Related Events In Patients With Multiple Myeloma In The Era Of Novel Agents: Low Incidence Of Pathological Fractures After Treatment

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3090-3090 ◽  
Author(s):  
Evangelos Terpos ◽  
Nikolaos Kanellias ◽  
Lia A Moulopoulos ◽  
Dimitrios Christoulas ◽  
Andreas Koureas ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Rib Fractures ◽  
Novel Agents ◽  
First Line ◽  
Pathological Fractures ◽  
First Line Therapy ◽  
Line Therapy ◽  
Skeletal Related Events ◽  
First Relapse ◽  
Frontline Therapy

Abstract Skeletal-related events (SREs) which include pathological fractures, spinal cord compression (SCC) and a need for radiotherapy or surgery to bone are frequent complications of multiple myeloma (MM). Although, the frequency and characteristics of SREs in MM patients who received conventional chemotherapy (CC) or thalidomide-based regimens along with bisphosphonates (BPs) have been described, there are no data available in the era of proteasome inhibitors or novel IMiDs. Thus, we retrospectively evaluated the records of 400 consecutive patients with symptomatic MM (207M/193F, median age: 63 years) who were diagnosed, treated and followed in a single center. All patients had a whole body skeletal survey using conventional radiography at diagnosis and then at the time of relapse or whenever clinically indicated, while MRI of the spine and pelvis at diagnosis was available for 223 patients. Furthermore, we tested 125 patients for SNPs in genes that are involved in the biology of bone destruction: LRP5 (rs4988321), GC vitamin D (rs4588), TNFRSF11A (rs3018362), DKK1 (rs1569198), RANKL (rs9594759), OPG (rs6469804) and ERS1 (rs1038304). At diagnosis, the skeletal survey detected osteolytic disease in 284 (71%) patients. In MRI, 34.5% of the patients had focal, 40.5% diffuse, 21% normal, and 4% a variegated pattern of marrow involvement. SREs were observed in 167 (41.7%) patients at diagnosis: 104 (26%) patients presented with pathological fractures (87 with vertebral fractures, 18 with rib fractures and 17 with fractures of the long bones; 22 patients had both vertebral and long bone or rib fractures), while 22 (5.5%) patients required surgery to bone, 21 (5.2%) radiotherapy and 20 (5%) patients presented with SCC. The incidence of SREs was higher in patients with osteolytic lesions (49.5% vs. 24%, p<0.001) or abnormal MRI pattern (49.7% vs. 23.3%, p=0.001). However, we noted that approximately 1/4 patients without lytic lesions in plain X-rays or with normal MRI pattern presented with a SRE at diagnosis. Patients homozygous for RANKL polymorphism had lower incidence of osteolysis at diagnosis (14/28, 50%) versus all others (76%, p=0.009), suggesting that this polymorphism may protect bone loss in MM, as it has been suggested for normal population. Frontline therapy with IMiD-based regimens was given in 172 (43%) patients, while 80 (20%) patients received bortezomib-based regimens, 111 (27.7%) both IMiD and bortezomib (VTD or VRD) and 37 (9.2%) patients CC. BPs were given in all but 86 patients (21.5%) at diagnosis, mainly due to renal insufficiency; however, almost 60% of them (n=51) received BPs later in the course of their therapy. The vast majority (91%) of patients received zoledronic acid (ZA). Due to renal impairment, ZA was discontinued in 6 patients, while the dose was reduced in 44. During first line treatment, 7 (1.75%) patients developed a SRE: 2 on bortezomib- and 5 on IMiD-based regimens. The rate of SREs was higher in patients who did not receive upfront BPs (4.7% vs. 1%; p=0.021). The median follow-up was 39 months. At the time of first relapse (data available for 176 patients), 3 patients presented with fractures and 35 patients required local radiotherapy to bone (SRE incidence: 21.6%). Patients who had received only bortezomib-based regimens (VD or VCD, n=20) had lower SRE rate (2/20, 10%) vs. all others (36/156, 22%, p=0.173); the 3 patients with fractures had received MPT (n=2) or RD (n=1). In total, during the course of their disease, 52.8% of the patients presented with at least one SRE. Presentation with SREs at diagnosis did not predispose for SREs during the disease course, regardless of anti-myeloma treatment, possibly due to the low number of fractures and the higher number of radiation needed after frontline therapy. In summary, our data from the first systematic report on the incidence and characteristics of SREs in the era of novel agents indicate that SREs remain a significant complication in MM. Importantly, despite high response rates after first line therapy more than 20% of patients required radiotherapy at the time of relapse. The fracture rate was very low during first line therapy and at first relapse probably due to the extensive use of potent BPs and bortezomib, which has bone anabolic effects. The use of modern imaging techniques (i.e. PET/CT or LDWBCT) that can detect bone masses earlier and lead to earlier initiation of treatment may reduce the SRE incidence in the near future. Disclosures: No relevant conflicts of interest to declare.

Lapatinib plus letrozole compared with letrozole alone as first-line therapy in hormone receptor positive HER2+ metastatic breast cancer (MBC): A quality-of-life (QOL) analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1039-1039 ◽  
Author(s):  
B. N. Sherif ◽  
B. Sherrill ◽  
M. Amonkar ◽  
Y. Wu ◽  
J. Maltzman ◽  
...  
Keyword(s):  
Hormone Receptor ◽  
Patient Population ◽  
Metastatic Breast ◽  
Analysis Of Covariance ◽  
Phase Iii ◽  
First Line ◽  
First Line Therapy ◽  
Hormone Receptor Positive ◽  
Line Therapy ◽  
The Impact

1039 Background: A phase III randomized double-blind multicenter trial compared lapatinib plus letrozole (L+Let) with letrozole plus placebo (Let), as first-line therapy for hormone receptor positive (HR+) MBC. Median PFS, the primary endpoint of the study, in patients who were HER2+ was significantly prolonged for L+Let compared with Let (8.2 vs 3 months, Hazard Ratio (95% CI)=0.71(0.53,0.96), p=0.019). This analysis focuses on the impact of treatments on QOL in the HER2+ subgroup. Methods: QOL outcomes included the Functional Assessment of Cancer Therapy-Breast (FACT-B) total, FACT-general (FACT-G), and trial outcome index (TOI) scores assessed at screening, every 12 weeks and at withdrawal. Higher scores indicate better QOL. Changes from baseline were analyzed using analysis of covariance. In a responder analysis, patients achieving minimally important differences in QOL scores (QOL responders) were compared with Fisher's exact test. Results: Among 1,286 patients, 219 were identified as HER2+ (L+Let n=111; Let n=108). Baseline QOL scores were comparable in the two arms. In this population, mean changes in subscale and total QOL scores were generally stable over time in both treatment arms for patients who stayed on study. For example, on the FACT-B, the average change from baseline in both groups was positive at all scheduled visits through Week 48 and the maximum difference between arms was 2.6 points (CI: -5.8, 11). There were no significant differences between the two treatment arms in percentage of QOL responders (Table). Conclusions: The addition of lapatinib to letrozole significantly increases PFS while maintaining QOL when compared with letrozole alone thus confirming the clinical benefit of the combination therapy in the HR+, HER2+ MBC patient population. This combination provides an effective option in this patient population by maintaining QOL and delaying the need for chemotherapy and its accompanying side effects. [Table: see text] [Table: see text]

Modified FOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizumab beyond first progression in advanced colorectal cancer: CCOG-0801 study.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 641-641
Author(s):  
Kiyoshi Ishigure ◽  
Goro Nakayama ◽  
Keisuke Uehara ◽  
Hiroyuki Yokoyama ◽  
Akiharu Ishiyama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Bleeding Event ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
To Receive

641 Background: Bevacizumab provides survival benefit as the first-line and second-line therapies in metastatic colorectal cancer (mCRC). A large observational study suggested use of bevacizumab beyond first progression (BBP) improved survival. This prompted us to conduct a multicenter phase II study of mFOLFOX6 plus bevacizumab followed by FOLFIRI plus bevacizimab in mCRC to further explore the strategy of BBP in Japanese patients. Methods: Previously untreated patients with assessable disease were treated with mFOLFOX6 plus bevacizumab until tumor progression, followed by FOLFIRI plus bevacizumab. The primary endpoint of the study was the second progression-free survival (2nd PFS), defined as duration from enrollment until progression after the second-line therapy. If the patient failed to receive the second-line treatment due to medical reasons or refusal, the PFS during the first-line therapy was used for analysis. Secondary endpoints were PFS, overall survival (OS), response rate (RR), disease control rate (DCR) and safety. Results: In the first-line therapy, 47 patients treated with mFOLFOX6 plus bevacizumab achieved RR of 61.7%, DCR of 89.4% and median PFS of 11.7 months. Thirty patients went on to receive the second-line therapy with FOLFIRI plus bevacizumab and achieved RR of 27.6%, DCR of 62.1%, and median PFS of 6.0 months. Median 2nd PFS was 16.2 months. Median survival time did not reach the median follow-up time of 27.4 months. Severe adverse events associated with bevacizumab during the first-line therapy were a venous thromboembolic event in one case (2%), a grade 2 bleeding event in one case (2%) and GI perforation in one case (2%). However, no critical events associated with bevacizumab were reported during the second-line therapy. Conclusions: The planned continuation of bevacizumab during the second line treatment is feasible in Japanese mCRC patients. A prospective randomized control study to confirm the efficacy has to be conducted in the future.

scholarly journals Bendamustine Adversely Affects Stem Cell Mobilization Among Patients with Mantle Cell Lymphoma (MCL): A Comparison of the BR Vs RCHOP Eras in British Columbia (BC), Canada

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4556-4556
Author(s):  
Hatem Alahwal ◽  
Parv Chapani ◽  
Diego Villa ◽  
Yasser Abou Mourad ◽  
Maryse Power ◽  
...  
Keyword(s):  
Stem Cell ◽  
Platelet Count ◽  
Univariate Analysis ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Risk Of Failure ◽  
Increased Risk ◽  
Cd34 Cells ◽  
Frontline Therapy

Abstract Introduction In 2013, bendamustine/rituximab (BR) replaced RCHOP as standard first line treatment for both transplant eligible and ineligible MCL patients (pts) in BC. Retrospective cohort studies report that bendamustine has no adverse effect on peripheral blood stem cell (SC) mobilization but this is discordant with local experience. We sought to compare rates of failed SC collection in MCL pts planned for high dose chemotherapy and autologous stem cell transplant (ASCT) after BR or RCHOP and identify risk factors for failed SC mobilization and collection. Methods We identified all pts with MCL in BC treated with BR or RCHOP as first line therapy who underwent SC mobilization from Jan. 1 2003-Dec. 31 2017 using the Leukemia/Bone Marrow Transplant Program of BC and Apheresis Database Standard mobilization was with G-CSF alone (G) until difficulties with SC collection were noted after BR. Different mobilization strategies were then used, including delaying SC collection 2-3 mos after BR, G + cyclophosphamide (G+C) mobilization and/or "rescue" plerixafor if Day 1 SC collection was inadequate. Failure of SC collection was defined as yield <1 x106 CD34+ cells/kg on apheresis Day 1 (D1fail). . All variables significant in univariate analysis (P<0.1) were entered into a multivariate analysis (MVA) logistic regression model to identify factors associated with D1 fail. Results A total of 152 pts were identified. 2 were excluded as they had pre-emptive plerixafor prior to apheresis D1 on a trial. Of the remaining 150 pts, 55 (37%) received BR, 95 (63%) RCHOP for a median of 6 cycles (range 1-6). Baseline characteristics were similar between groups (Table 1). Pts receiving BR had higher remission rates compared to RCHOP (CR 58% vs 35%, P=.004) and a longer duration from their last chemotherapy to apheresis D1 (BR 89 d vs RCHOP 39 d, P<0.), reflecting an intentional change in practice. For this same reason, use of G+C mobilization was higher in BR pts (45%) compared with RCHOP pts (1%). Failure on D1 of SC collection was significantly higher after BR compared to RCHOP (45% vs. 10%, P<.001). This difference persisted when only pts mobilized with G alone were included: D1fail 60% BR vs 10% RCHOP (P<.001), Fig. 1. Among BR pts, D1fail was higher for those mobilized with G compared with G+C (60% vs. 28%, P=.03). Of the 25 BR pts with D1fail, 20 pts received rescue plerixafor (P) (1 dose: 18, 2 doses: 1, 3 doses: 1) with 17 successfully collecting > 2.0 x106 CD34+ cells/kg, 2 successfully collected after a 2nd round of SC mobilization (Pt1: G+C+P, Pt2: G+P), and 1 pt did not undergo ASCT due to collection failure. Of the 5 pts who did not receive plerixafor, 2 successfully collected with 1-2 additional apheresis days and 3 successfully collected with a 2nd round of SC mobilization (2: G+P, 1: G+C). Among the 9 RCHOP pts with D1fail, 1 had rescue plerixafor with success, 3 successfully collected after 1-2 more apheresis days and 5 had a 2nd round of SC mobilization (1: G, 4: G+P), of which 1 failed and did not proceed to ASCT. Univariate analysis identified the following associated with D1fail: frontline therapy (BR vs RCHOP, P=<.001), mobilization regimen (G+C vs G, P=.001), gender (P=.002) and D1 platelet count (P=<.001). Delaying SC mobilization in pts who received BR did not improve D1 yield (P=.31). In MVA, frontline therapy with BR had an increased risk of D1fail compared to RCHOP with an odds ratio (OR) of 7.83 (95% CI 2.7-23.1), P<.001. Using G+C significantly improved the odds of a successful collection compared to G alone (OR for D1fail 0.17 [95% CI 0.05-0.62], P=.007). Female gender and low platelet count also increased risk of D1fail in MVA (Table 2). Conclusion MCL pts who receive BR as first line therapy have an almost 8-times higher risk of failure of D1 SC collection compared to those who receive RCHOP. This failure can be overcome largely with "rescue" plerixafor and partially with planned G+C mobilization such that successful collection can be achieved in >90% of pts. However, these agents add cost and potential toxicity. Platelet count on D1 SC collection is a potential indicator of high risk of failure. Delaying SC mobilization in BR pts does not improve collection yield. The impact of bendamustine in pre-transplant chemotherapy regimens, not only for MCL but also for a broad range of lymphomas where it is being increasingly used, must be considered when planning SC mobilization strategies. Disclosures Sehn: Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Lundbeck: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria; Roche/Genentech: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Celgene: Consultancy, Honoraria.

scholarly journals Use of crizotinib for refractory ALK-positive lymphomas

2017 ◽  
Vol 89 (7) ◽  
pp. 51-56 ◽  
Author(s):  
L N Shelikhova ◽  
V V Fominykh ◽  
D S Abramov ◽  
N V Myakova ◽  
M A Maschan ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Cell Lymphoma ◽  
Large Cell ◽  
First Line ◽  
Hematopoietic Stem ◽  
First Line Therapy ◽  
Line Therapy ◽  
Positron Emission ◽  
Before And After ◽  
Alk Positive

Aim. To evaluate the safety and efficacy of crizotinib used in pediatric patients with relapsed or refractory ALK-positive anaplastic large-cell lymphoma (ALCL). Subjects and methods. The paper describes the experience with crizotinib used in 8 patients with refractory ALK-ALCL before and after allogeneic hematopoietic stem cell transplantation (HSCT). Results. All the 8 (100%) patients treated with crizotinib were recorded to have complete responses, including complete metabolic ones (tumor disappearance as evidenced by positron emission tomography (PET)/computed tomography. Conclusion. Low and manageable toxicity of crizotinib and complete PET-negative responses in patients with resistant ALK lymphomas favor the need to test the drug as first-line therapy, by possibly decreasing the intensification of chemotherapy.

scholarly journals Outcomes of Plasma Cell Leukemia Patients in the Era of Next-Generation Novel Agents: A Single-Center Retrospective Cohort Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 6-7
Author(s):  
Alex Ge ◽  
Chiung-Yu Huang ◽  
Thomas Martin ◽  
Jeffrey L. Wolf ◽  
Nina Shah ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Research Funding ◽  
Progression Free Survival ◽  
Novel Agents ◽  
Next Generation ◽  
First Line ◽  
Advisory Committees ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy

Introduction Primary plasma cell leukemia (pPCL) is a rare and aggressive disease comprising 1-5% of all plasma cell dyscrasias. Although historically pPCL has been defined by circulating plasma cells (CPCs) ≥ 20% and 2.0 × 109/L, many series require only one of these two criteria for diagnosis. Over time there has been a pressing need to change the definition further in order to capture patients at an earlier stage of the disease. Recent studies have shown that multiple myeloma (MM) patients who have CPCs ≥ 5% but &lt; 20% at diagnosis have similarly poor outcomes. These thresholds for defining pPCL have not been studied in the current era of novel agents. While bortezomib-based regimens have been shown to extend pPCL patient survival, studies with next-generation agents such as carfilzomib (CFZ), pomalidomide, and daratumumab (DARA) are still scarce. Methods We performed a single-center, retrospective study of patients who at diagnosis had pPCL (defined as CPCs ≥ 20% or 2.0 × 109/L) or had MM with &lt; 20% CPCs (MM-CPC). Patients were treated at our institution between 1/1/2000-7/17/2020. Overall response rates were determined according to International Myeloma Working Group criteria. Overall survival (OS) was defined as the length of time between initiation of first line therapy and death. Progression-free survival (PFS) was defined as the length of time between initiation of first line therapy and first progression. OS and PFS were compared using log-rank tests. Results Of the 54 patients identified, 38 had pPCL and 16 had MM-CPC. The median age at diagnosis of the pPCL and MM-CPC groups were 59.2 (range 43-94) and 59.8 years (range 29-79), respectively, with a similar percentage of females, 47.4% vs. 37.5%. Both groups were similarly distributed by year of diagnosis; 76.3% and 62.5% of pPCL and MM-CPC patients were diagnosed between 2012-2020, respectively. The pPCL cohort had median CPCs of 40% (15-98) while the MM-CPC cohort had median CPCs of 4% (1-15). Median CPCs at diagnosis was 3.36 (0.44-179) × 109/L in the pPCL group compared to 0.33 (0.04-1.79) × 109/L in the MM-CPC group. Most patients for both groups were ISS stage III at diagnosis (57.9% in pPCL cohort, 56.2% in MM-CPC cohort). R-ISS assessment was not feasible due to missing data. A greater proportion of patients in the pPCL group (44.7%) had complex cytogenetics at diagnosis compared to the MM-CPC group (25.0%). All patients were exposed to at least one novel agent over the entire disease course. Of these patients, 50 (92.6%) were exposed to bortezomib, 45 (83.3%) to lenalidomide, 33 (61.1%) to CFZ, 22 (40.7%) to DARA, 13 (24.1%) to pomalidomide, and 4 (7.4%) to venetoclax. Twenty-four patients (44.4%) received an autologous stem cell transplant (ASCT). At the best response to treatment, 76.7%, 62.8% and 37.9% of patients achieved a partial response or greater to first, second and third line therapy, respectively. The median OS of the pPCL and MM-CPC groups was 34.5 and 35.5 months (p = 0.97) (Figure 1A), while the median PFS was 13.9 and 10.9 months (p = 0.52) (Figure 1B), respectively. The median follow-up was 28.1 months. No differences were observed for patients with CPCs &lt; 20% compared to patients with CPCs ≥ 20% (p = 0.98). There was trend towards a better survival for patients with CPCs &lt; 2 × 109/L compared to CPCs ≥ 2 × 109/L (p = 0.35). Since we did not observe any meaningful difference in OS or PFS between the pPCL and MM-CPC groups, we combined these groups for further survival analysis. Patients exposed to either DARA or CFZ (n = 37) had a median OS of 59.2 months, while patients exposed to neither drug (n = 17) had a median OS of 11.7 months (p = 0.02) (Figure 1C). ASCT was associated with a prolonged median OS (66.8 months vs. 17.2 months, p = 0.0001) (Figure 1D), while a complex karyotype at diagnosis was associated with a poorer median OS (17.4 months vs. 66.8 months, p = 0.01). Conclusions In the era of next-generation novel agents, overall and progression-free survival of pPCL and MM-CPC patients are similar. Patients exposed to DARA or CFZ have an improved survival compared to those who did not receive these drugs. ASCT is also associated with a superior survival over those who did not receive a transplant. Further studies are needed to evaluate the efficacy of these next-generation drugs in this patient population. Disclosures Martin: Janssen: Research Funding; Seattle Genetics: Research Funding; AMGEN: Research Funding; GSK: Consultancy; Sanofi: Research Funding. Wolf:Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Shah:GSK, Amgen, Indapta Therapeutics, Sanofi, BMS, CareDx, Kite, Karyopharm: Consultancy; BMS, Janssen, Bluebird Bio, Sutro Biopharma, Teneobio, Poseida, Nektar: Research Funding. Wong:Sanofi: Membership on an entity's Board of Directors or advisory committees; Fortis: Research Funding; Roche: Research Funding; Janssen: Research Funding; Amgen: Consultancy; GSK: Research Funding; Bristol Myers Squibb: Research Funding.

scholarly journals Patient Profile and Treatment Patterns in a Commercially Insured Population with Follicular Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5880-5880
Author(s):  
Nathan H Fowler ◽  
Yanni Hao ◽  
Stephen Lim ◽  
Guifang Chen ◽  
Frank Li ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Second Line ◽  
First Line ◽  
Advisory Committees ◽  
First Line Therapy ◽  
Line Therapy ◽  
Third Line ◽  
Line Of Therapy

Introduction: Follicular lymphoma (FL) is the most common indolent non-Hodgkin lymphoma in the Western hemisphere. Patient characteristics and burden of FL are incomplete and vary from previous studies. This study evaluated patient profile, including patient characteristics, treatment patterns, and duration using real-world data. Methods: Using the Truven MarketScan® databases, patients with FL who were newly initiated with FL indicated regimens were identified from 1/1/2010-12/31/2013 (initial treatment identification period). Patients were selected if they were ≥18 years old, had 1 FL ICD-9 code (202.0) as primary or secondary diagnosis, at least 1 FL commonly prescribed systemic anti-cancer therapy after the diagnosis, and did not use any FL indicated regimen in the past 6 months prior to first agent included in the initial treatment identification period. These patents were followed ≥3 months or to June 30, 2018. Primary outcomes were the distribution of regimens by line, the number of patients who switched from first- to second-line therapies, and from second- to third-line therapies. The treatment duration by line of therapy and regimen were also analyzed. Discontinuation was defined as 3 months without receiving a regimen after treatment. Results: This study identified 4,970 patients who initiated treatment for FL. Of these patients, 48.1% were female (n=2,390), with a mean age of 62.0 (SD: 14.0) years. The average follow-up time was approximately 2 years (median: 733 days). In this analysis, 4,970 patients with FL received first-line therapy for 153 days (median: 94 days), 1,985 received second-line therapy (39.9% of patients who received first-line therapy) for 208 days (median: 80 days), and 664 received third-line therapy (13.4% of patients who received first-line therapy) for 117 days (median: 43 days). Of the 4,970 patients on first-line therapy, 453 (9.1%) remained on first-line therapy, 2,532 (51.0%) discontinued treatment, and 1,985 (39.9%) patients switched to the next line of therapy during the follow-up period. Of the 1,985 patients who switched to second-line therapy, 328 (16.5%) remained by the end of follow-up period, 993 (50.0%) discontinued, and 664 (33.4%) switched to the next line of therapy during the follow-up period. Of the 664 patients who switched to third-line therapy, 125 (18.8%) remained, 269 (40.5%) discontinued, and 270 (40.7%) switched to the next line of therapy. The most common first-line regimens in descending order received by patients were rituximab (n=1,478, 29.7%), R-CHOP (n=1,368, 27.5%), BR (n=1,050, 21.1%), R-CVP (n=371, 7.5%), and FCR (n=63, 1.3%). Second-line treatment regimens were (N=1,985) rituximab (n=992, 50.0%), BR (n=202, 10.2%), R-CHOP (n=138, 7.0%), and R-CVP (n=120, 6.1%). Third-line treatment regimens were (N=664) rituximab (n=228, 34.3%), BR (n=91, 13.7%), R-CHOP (n=75, 11.3%), cyclophosphamide (n=35, 5.3%) and R-CVP (n=31, 4.7%). Conclusion: This data set describes the percentage of patients that transition from first- to second-line and second- to third-line treatment for FL. The primary regimens used across the treatment lines conform to those recommended by the NCCN guidelines. In addition, smaller numbers of non-recommended regimens were reported. Disclosures Fowler: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; ABBVIE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Hao:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Lim:Novartis Pharmaceuticals Corporation: Employment. Chen:Novartis Pharmaceuticals Corporation: Consultancy, Employment. Li:Novartis Pharmaceuticals Corporation: Employment. Arcona:Novartis Pharmaceuticals Corporation: Employment.

scholarly journals Optimizing Deep Response Assessment for AL Amyloidosis Using Involved Free Light Chain Level at End of Therapy

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3227-3227
Author(s):  
Eli Muchtar ◽  
Angela Dispenzieri ◽  
Nelson Leung ◽  
Francis K. Buadi ◽  
David Dingli ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Light Chain ◽  
Research Funding ◽  
Response Assessment ◽  
Al Amyloidosis ◽  
First Line ◽  
Advisory Committees ◽  
First Line Therapy ◽  
Line Therapy ◽  
Organ Response

Abstract Introduction: Light chain burden in light chain (AL) amyloidosis is often low, making accurate response assessment challenging. Methods: AL amyloidosis patients achieving very good partial or complete response to first line therapy and had serial sFLC studies during and after completion of therapy were included (n=396). Involved free light chain (iFLC), difference in involved-to-uninvolved free light chains (dFLC) and sFLC ratio (sFLCR) were assessed at the end of first line therapy and at nadir iFLC. Survival analysis was done using the Kaplan-Meier method. Hematological progression-free survival (hemPFS) was defined as the time from diagnosis until hematological progression or death, where patients known to be alive and progression-free at the end of follow-up were censored. Hematological progression was defined according to consensus criteria or upon initiation of second line therapy, whichever came first. Results: The median iFLC and dFLC at the end of therapy was 1.7 mg/dL and 0.5 mg/dL, respectively. sFLCR normalization occurred in 70% of patients. iFLC ≤2 mg/dL and dFLC ≤0.5 mg/dL were associated with a longer hemPFS compared to their counterparts (Figure). Only iFLC ≤2 mg/dL was associated with a significantly longer overall survival (Figure). sFLCR normalization did not predict hemPFS or overall survival. Organ response was predicted by iFLC ≤2 mg/dL and dFLC ≤0.5 mg/dL (Table), with best discrimination seen with iFLC ≤2 mg/dL. Organ response was not predicted by sFLC normalization (Table). The median nadir iFLC was 1.4 mg/dL and was reached 3.9 months from the end of therapy, longer in transplanted patients compared to patients treated with non-transplant regimens (7.3 vs 1.8 months, respectively; P<0.001). iFLC ≤2 mg/dL at the completion of therapy and nadir iFLC reached >12 months from the end of therapy were favorable predictors of hemPFS/OS in a multivariate analysis. Conclusion: iFLC at the end of first line therapy better predicts for organ response and survival than dFLC among deep responders. Normalization of sFLCR does not predict for organ response or survival and should not be used as measure of therapeutic efficacy. Figure. Figure. Disclosures Dispenzieri: Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding. Dingli:Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Millennium Takeda: Research Funding; Millennium Takeda: Research Funding. Kapoor:Celgene: Research Funding; Takeda: Research Funding. Russell:Vyriad: Equity Ownership. Kumar:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding. Gertz:Alnylam: Honoraria; celgene: Consultancy; Ionis: Honoraria; Abbvie: Consultancy; annexon: Consultancy; janssen: Consultancy; spectrum: Consultancy, Honoraria; Research to Practice: Consultancy; Medscape: Consultancy; Apellis: Consultancy; Teva: Consultancy; Amgen: Consultancy; Prothena: Honoraria; Physicians Education Resource: Consultancy.

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