Bendamustine-Rituximab (BR) Replaces R-CHOP As “Standard of Care” in the Treatment of Indolent Non-Hodgkin Lymphoma in German Hematology Outpatient Centres

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3666-3666 ◽  
Author(s):  
Wolfgang Ulrich Knauf ◽  
Wolfgang Abenhardt ◽  
Arnd Nusch ◽  
Renate Grugel ◽  
Norbert Marschner
Keyword(s):  
Hodgkin Lymphoma ◽  
Real Life ◽  
Stage Iv ◽  
Standard Of Care ◽  
Low Grade ◽  
Line Treatment ◽  
Clinical Registry ◽  
Non Hodgkin Lymphoma ◽  
Systemic Treatments ◽  
The Impact

Abstract Abstract 3666 Introduction With the FDA and EMA approval of Bendamustine a new treatment option has recently become available to patients (pts) with indolent (low-grade) non-Hodgkin lymphoma (iNHL). Clinical registries provide insight into real-life treatment of pts. They can help to answer the question whether patients may benefit from new research findings. Methods The clinical registry on lymphoid neoplasms (TLN Registry), conducted by iOMEDICO in collaboration with the Arbeitskreis Klinische Studien (AKS) and the Kompetenznetz Maligne Lymphome (KML), prospectively collects data on the treatment of pts with lymphoid B-cell neoplasms as administered in hematology outpatient centres in Germany. Pts are followed for 5 years. A broad set of data regarding patient and tumor characteristics, comorbidities, all systemic treatments, response rates, progression-free survival and overall survival are recorded. Since May 2009, 106 sites have actively recruited a total of 2579 pts. Results From the overall sample, 645 pts received systemic 1st-line treatment for indolent Non-Hodgkin lymphoma (iNHL). 53% of pts are male, mean age at time of primary diagnosis was 65 years (yrs) and at start of therapy 66 yrs. Tumor stage was 7% Stage I, 15% Stage II, 25% Stage III and 54% Stage IV. 61% of pts (n=387) were diagnosed with at least one comorbidity, mainly hypertension (33%) or diabetes (12%); the average Charlson Comorbity Index of 0.6 indicates that pts have few comorbities. Rituximab is part of the 1st-line treatment in 94% (n=606) of pts with iNHL. Bendamustine is part of the 1st-line treatment in 71% (n=455) of pts with iNHL. It is mostly applied in combination with Rituximab (BR, 66%, n=428). Further 2% (n=10) receive Bendamustin as monotherapy. Rituximab/Cyclophosphamide/Doxorubicin/Vincristine/Prednisone (R-CHOP) as 1st-line treatment is applied in 16% (n=105) of pts with iNHL. Pts receiving BR or R-CHOP differ. Pts characteristics indicate that BR is applied preferably in elderly pts (mean 67.3 vs. 60.9 yrs). However, BR is the preferred treatment also in pts younger than 66 yrs (60% vs. 23%). The use of BR has increased from 62% in 2009 to 68% in 2011, whereas the rate of R-CHOP has decreased from 19% in 2009 to 15% in 2011. Of all pts with iNHL, 121 have received 2nd-line treatment. Rituximab is part of the 2nd-line treatment in 84% (n=102) of pts with iNHL. Bendamustine is part of the 2nd-line treatment in 68% (n=82) of pts with iNHL. It is mostly applied in combination with Rituximab (BR, 60%, n=72). Further 7% (n=9) receive Bendamustin as monotherapy. R-CHOP as 2nd-line treatment is applied in 7% (n=9) of pts with iNHL. Conclusion BR is the most frequently used systemic treatment for pts with iNHL in German hematology outpatient centres. The use of BR has continuously increased since 2009. In contrast, the use of R-CHOP has decreased. This indicates that in Germany R-CHOP can no longer be considered as “standard of care” for pts with iNHL. These data also show that results from clinical trials are quickly implemented into daily practice. The impact of BR on quality of life and survival remains to be of central interest in the future. Disclosures: Knauf: Mundipharma GmbH: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Bendamustine Replaces Chlorambucil As “Standard of Care” in the Treatment of Elderly Patients with Chronic Lymphocytic Leukemia in German Hematology Outpatient Centres

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4605-4605
Author(s):  
Wolfgang Ulrich Knauf ◽  
Wolfgang Abenhardt ◽  
Arnd Nusch ◽  
Renate Grugel ◽  
Norbert Marschner
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Treatment Options ◽  
Real Life ◽  
Standard Of Care ◽  
Lymphocytic Leukemia ◽  
Line Treatment ◽  
Clinical Registry ◽  
Systemic Treatments ◽  
New Treatment ◽  
The Impact

Abstract Abstract 4605 Introduction With the FDA and EMA approval of Bendamustine and Rituximab new treatment options have recently become available to patients (pts) with chronic lymphocytic leukemia (CLL). Clinical registries provide insight into real-life treatment of pts. They can help to answer the question whether patients may benefit from new research findings. Methods The clinical registry on lymphoid neoplasms (TLN Registry), conducted by iOMEDICO in collaboration with the Arbeitskreis Klinische Studien (AKS) and the Kompetenznetz Maligne Lymphome (KML), prospectively collects data on the treatment of pts with lymphoid B-cell neoplasms as administered in hematology outpatient centres in Germany. Pts are followed for 5 years. A broad set of data regarding patient and tumor characteristics, comorbidities, all systemic treatments, response rates, progression-free survival and overall survival are recorded. Since May 2009, 106 sites have actively recruited a total of 2579 pts. Results From the overall sample, 420 pts received systemic 1st-line treatment for CLL. 65% of pts are male, mean age at time of primary diagnosis was 66 years (yrs) and at start of therapy 69 yrs. Tumor stage was 20% Binet A, 35% Binet B and 45% Binet C. 68% of pts (n=285) were diagnosed with at least one comorbidity, mainly hypertension (37%) or diabetes (15%); the average Charlson Comorbity Index of 0.7 indicates that overall pts have few comorbities. Rituximab is part of the 1st-line treatment in 82% (n=345) of pts with CLL. Bendamustine is part of the 1st-line treatment in 59% (n=247) of pts with CLL. It is mostly applied in combination with Rituximab (BR, 51%, n=213). Further 7% (n=28) receive Bendamustin as monotherapy. Fludarabine is part of the 1st-line treatment in 31% (n=132) of pts with CLL. It is applied in combination with Cyclophosphamide and Rituximab (FCR, 25%, n=103), as monotherapy (4%, n=15) or in combination with Cyclophosphamide (FC, 1%, n=6). Chlorambucil is part of the 1st-line treatment in 7% (n=31) of pts with CLL. It is applied as monotherapy (4%, n=15) or in combination with Rituximab (2%, n=10). Pts receiving BR, FCR or Chlorambucil differ. Pts characteristics indicate that BR and Chlorambucil are applied preferably in elderly pts (mean 70.1 (BR) vs. 75.7 (Chlorambucil) vs. 63.4 (FCR) yrs). Also, BR is given preferably in advanced stages of the disease as compared to FCR (Binet C 49% vs. 34%). The use of BR has increased from 41% in 2009 to 57% in 2011, while the use of FCR has decreased from 33% in 2009 to 17% in 2011. Of all pts with CLL in the TLN, 181 have received 2nd-line treatment. Rituximab is part of the 2nd-line treatment in 76% (n=137) of pts with CLL. Bendamustine is part of the 2nd-line treatment in 66% (n=120) of pts with CLL. It is mostly applied in combination with Rituximab (BR, 56%, n=101). Further 10% (n=18) receive Bendamustin as monotherapy. Fludarabine is part of the 2nd-line treatment in 20% (n=37) of pts with CLL. It is applied in combination with Cyclophosphamide and Rituximab (FCR, 10%, n=18), as monotherapy (5%, n=9) or in combination with Cyclophosphamide (FC, 3%, n=5). Chlorambucil is part of the 2nd-line treatment in 4% (n=7) of pts with CLL. It is mostly applied in combination with Rituximab (2%, n=4). Conclusion Rituximab and Bendamustine are the most frequently used drugs for the treatment of CLL in German hematology outpatient centres. The use or BR has significantly increased since 2009. In contrast, the use of FCR has decreased and only a minority of pts receive Chlorambucil. This indicates that in Germany Chlorambucil is no longer considered the “standard of care” for elderly pts with CLL. These data also show that results from clinical trials are quickly implemented into daily practice. The impact of these new treatment options on quality of life and survival remains to be of central interest in the future. Disclosures: Knauf: Mundipharma GmbH: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Fludarabine, Mitoxantrone and Dexamethasone for the First Line Treatment of Patients with Indolent Non-Hodgkin Lymphoma (NHL): GATLA First Interim Report (Grupo Argentino de Tratamiento de la Leucemia Aguda).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4680-4680
Author(s):  
Gustavo Milone ◽  
A. Rodriguez ◽  
Jorge Milone ◽  
R.F. Bezares ◽  
S. Rudoy ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hodgkin Lymphoma ◽  
Response Rate ◽  
Response Rates ◽  
Low Grade ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
First Line Treatment

Abstract Background: fludarabine (F) is licensed for the management of indolent non-Hodgkin lymphoma in countries such as Canada and Switzerland. Clinical evidence suggests that fludarabine monotherapy is as least as effective, than conventional therapies such as cyclophosphamide, vincristine, prednisone (CVP) for the first and second line treatment of B-cell low grade NHL achieving objective response rates. Better response rates can be achieved combining F with Mitoxantrone (N) and Dexamethasone (D) in indolent NHL patients (pts). The GATLA (Grupo Argentino de Tratamiento de la Leucemia Aguda) started a prospective multicenter national study to evaluate the use FND as a first line treatment for low grade NHL. Aims: to assess the response rate, safety, disease free survival (DFS) and overall survival (OS) of FND as first line treatment for indolent NHL during (2002–2006). Methods: Ninety-six patients in the period of January 2002 to April 2006 were recruited. Sixty-nine patients were valuable at the time of analysis. Median age 54 years old (range: 21–79). Gender: male 51% and female 49%. Inclusion criteria for low grade NHL-LG was: non-previous, age > 18 years old with symptomatic disease, ECOG performance status 0–2 and written informed consent. Ann Arbor staging: 5,8%, 14,5%, 24,6% and 55%. FND treatment consisted of F 25 mg/m2 i.v. (days 1–3), N 10 mg/m m2 i.v. (day 1) and D 20 mg (days 1–5) each 28 days for 6 cycles. All patients received oral antibiotics for intestinal decontamination, antifungal prophylaxis and Trimethoprim-Sulfamethoxazole as P. carinii prophylaxis for one year. Results: on this low grade NHL cohort the overall response rate (ORR) was 93% (ORR) with 70% (48 pts) with complete response (CR) and 23% (16 pts) with partial response; progressive disease and non-response 7% (5 pts). The probability of event free survival (EFS) and overall survival (OS) at 24 months was 60% and 90% respectively. Two patients developed secondary malignancies after treatment and one died. Only one patient died in CR. Conclusions: in this population FND treatment demonstrate a high CR rate with low toxicity and high probability of EFS and OS as previous experience published in the literature.

Efficacy and safety of CAR19/22 T-cell “cocktail” therapy in patients with refractory/relapsed B-cell non-Hodgkin lymphoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2534-2534
Author(s):  
Liang Huang ◽  
Na Wang ◽  
Chunrui Li ◽  
Yi Xiao ◽  
Yang Cao ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Low Grade ◽  
Efficacy And Safety ◽  
T Cell Therapy ◽  
Overall Response ◽  
Non Hodgkin Lymphoma ◽  
The Impact

2534 Background: Antigen escape relapse has emerged as a major challenge for long-term disease control post CD19-directed therapies, to which dual-targeting of CD19 and CD22 has been proposed as a potential solution. Methods: Between Mar 2016 and Jan 2018, we conducted a pilot study (ChiCTR-OPN-16008526) in 38 patients (pts), who had refractory/relapsed B-cell non-Hodgkin lymphoma (B-NHL), to evaluate the efficacy and safety of sequential infusion of anti-CD19 and anti-CD22, two single-specific, third-generation CAR19/22 T-cell “cocktail”. The cutoff date for data collection was Apr 30, 2018. Results: At a minimum follow-up of 3 months (mos), 26 of the 36 evaluable pts achieved an overall response (ORR), including 18 with a complete response (CR) and 8 with a partial response (PR). The ORR at mo 3 was consistent in different subgroups, irrespective of pathologic subtypes, cell of origin, cytogenetic or genomic aberrations. At the data cutoff, 15 of the 18 pts who had a CR at mo 3 maintained their responses, 2 of 8 pts who had a PR within 3 mos continued to have a CR without additional therapies. Collectively, the best ORR was 83.3%, with a best CR rate of 55.5% and a best PR rate of 27.8%. With a median follow-up of 5.3 mos (range, 0.4 to 16.2), the median PFS was 5.8 mos, and the median OS was not reached (NR). Pts received therapy at first relapse had better PFS than those who received therapy at the time with primary refractory diseases or at multiple relapses. Notably, pts who achieved an overall response at mo 3 (R3m) had significantly extended PFS and OS when compared with pts who did not. Repeated biopsy and IHC was conducted in 3 of the 13 pts. However, loss of CD19 or CD22 was not detected. Of the 9 pts with IgH/MYC translocation, with a median follow-up of 10.1 mos, the median PFS and median OS were NR. At data cutoff, 7 pts who had achieved R3m maintained their responses, including all the 4 pts with double-hit lymphoma. However, of the 10 pts with del(17p) or TP53 mutation, with a median follow-up of 5.3 mos (range, 2.7 to 14.5), the median PFS was 3.6 mos and the median OS was 9.9 mos. All pts experienced reversible CRS, with 21.1% were of high-grade. Neurotoxicity developed in 13.2% pts and were all low-grade. Conclusions: Our results indicated that sequential infusion of CAR19/22 T-cell is efficient and safe for pts with B-NHL. Dual antigen targeting is a promising approach to circumvent antigen loss relapse after CAR T-cell therapy. The impact of genetic subtypes and clinical parameters further underscores the critical importance of personalized immunotherapies. Clinical trial information: ChiCTR-OPN-16008526.

scholarly journals Immunotherapy in Hodgkin Lymphoma: Present Status and Future Strategies

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1071 ◽  
Author(s):  
Theodoros P. Vassilakopoulos ◽  
Chrysovalantou Chatzidimitriou ◽  
John V. Asimakopoulos ◽  
Maria Arapaki ◽  
Evangelos Tzoras ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Checkpoint Inhibitors ◽  
Stage Iv ◽  
European Medicines Agency ◽  
Line Treatment ◽  
Phase Ii Trials ◽  
First Line ◽  
Heavily Pretreated ◽  
The Impact ◽  
First Line Treatment

Although classical Hodgkin lymphoma (cHL) is usually curable, 20–30% of the patients experience treatment failure and most of them are typically treated with salvage chemotherapy and autologous stem cell transplantation (autoSCT). However, 45–55% of that subset further relapse or progress despite intensive treatment. At the advanced stage of the disease course, recently developed immunotherapeutic approaches have provided very promising results with prolonged remissions or disease stabilization in many patients. Brentuximab vedotin (BV) has been approved for patients with relapsed/refractory cHL (rr-cHL) who have failed autoSCT, as a consolidation after autoSCT in high-risk patients, as well as for patients who are ineligible for autoSCT or multiagent chemotherapy who have failed ≥ two treatment lines. However, except of the consolidation setting, 90–95% of the patients will progress and require further treatment. In this clinical setting, immune checkpoint inhibitors (CPIs) have produced impressive results. Both nivolumab and pembrolizumab have been approved for rr-cHL after autoSCT and BV failure, while pembrolizumab has also been licensed for transplant ineligible patients after BV failure. Other CPIs, sintilimab and tislelizumab, have been successfully tested in China, albeit in less heavily pretreated populations. Recent data suggest that the efficacy of CPIs may be augmented by hypomethylating agents, such as decitabine. As a result of their success in heavily pretreated disease, BV and CPIs are moving to earlier lines of treatment. BV was recently licensed by the FDA for the first-line treatment of stage III/IV Hodgkin lymphoma (HL) in combination with AVD (only stage IV according to the European Medicines Agency (EMA)). CPIs are currently being evaluated in combination with AVD in phase II trials of first-line treatment. The impact of BV and CPIs was also investigated in the setting of second-line salvage therapy. Finally, combinations of targeted therapies are under evaluation. Based on these exciting results, it appears reasonable to predict that an improvement in survival and a potential increase in the cure rates of cHL will soon become evident.

scholarly journals A Retrospective Analysis of the Efficacy of Low-Dose Metronomic Cyclophosphamide for Treatment in Patients with Low Grade Non-Hodgkin Lymphoma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1361-1361
Author(s):  
Boram Han ◽  
Bum Jun Kim ◽  
Ho Young Kim ◽  
Dae Young Zang ◽  
Hyun Lim ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Low Dose ◽  
Marginal Zone ◽  
Marginal Zone Lymphoma ◽  
Low Grade ◽  
Line Treatment ◽  
First Line ◽  
Non Hodgkin Lymphoma ◽  
Metronomic Cyclophosphamide ◽  
First Line Treatment

Abstract Background Low-dose metronomic cyclophosphamide chemotherapy is an emerging strategy offering a potentially less toxic yet effective treatment modality. We evaluated the efficacy and safety of low-dose metronomic cyclophosphamide in patients with low grade non-Hodgkin lymphoma (NHL) by retrospectively reviewing the data. Method The patients received oral cyclophosphamide (50 mg per day) and/or oral methotrexate (2.5 mg twice weekly) until disease progression or unacceptable toxicity was noted. Results Of the 36 patients, 17 (47.2%) were male, median age was 66.4 years (range, 37-91 years), and subtypes of NHL were mucosa associated lymphoid tissue lymphoma (55.6%), small lymphocytic lymphoma (13.9%), follicular lymphoma (11.1%), mantle cell lymphoma (8.3%), nodal marginal zone lymphoma (4.5%), splenic marginal zone lymphoma (2.8%), and lymphoplasmacytic lymphoma (2.8%). The stage I, II, III, IV were 38.9%, 13.9%, 11.1%, 36.1%, respectively and 55.6% of patients received this regimen as the first-line treatment, mainly due to frailty, refusal to standard chemotherapy. The overall best response rate (ORR) was 73.5% (12 complete responses, CRs and 13 partial responses, PRs), with 29.1 months of the median duration of response and the disease control rate was 88.2%. The median treatment duration was 8.8 months (range, 0.1-38.4 months); the median progression-free survival (PFS) was 43.5 months, and the median overall survival (OS) was not yet reached. Especially, the ORR in patients who were treated with metronomic cyclophosphamide as the first line treatment and as more than the second line treatment were 78.9% (10 CRs, 5 PRs) and 66.6% (2 CRs, 9 PRs), respectively. The median PFS were not reached in the first line cyclophosphamide treatment group and 26.5 months (range, 5.7-47.2 months) in the other group (p=0.110), and similarly, the median OS were not reached and 64.4 months (0-135.7 months) (p=0.058), respectively. The regimen was generally well tolerated, with small numbers of grade 3-4 toxicities; neutropenia (2%), anemia (3%), thrombocytopenia (3%), fatigue (4%), and anorexia (1%). Conclusion We concluded that low-dose metronomic cyclophosphamide represents efficacious and well-tolerated treatment for low-grade NHL patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Review of Treatment Options for the Management of Advanced Stage Hodgkin Lymphoma

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3745
Author(s):  
Hélène Vellemans ◽  
Marc P. E. André
Keyword(s):  
Hodgkin Lymphoma ◽  
New Drugs ◽  
Western World ◽  
Tumor Control ◽  
Advanced Stage ◽  
Line Treatment ◽  
First Line ◽  
Remission Rates ◽  
The Impact ◽  
First Line Treatment

Hodgkin lymphoma (HL) is a lymphoid-type hematologic disease that is derived from B cells. The incidence of this lymphoid malignancy is around 2–3/100,000/year in the western world. Long-term remission rates are linked to a risk-adapted approach, which allows remission rates higher than 80%. The first-line treatment for advanced stage classical HL (cHL) widely used today is doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc) chemotherapy. Randomized studies comparing these two regimens and a recently performed meta-analysis have demonstrated consistently better disease control with BEACOPPesc. However, this treatment is not the standard of care, as there is an excess of acute hematological toxicities and therapy-related myeloid neoplasms. Moreover, there is a recurrent controversy concerning the impact on overall survival with this regimen. More recently, new drugs such as brentuximab vedotin and checkpoint inhibitors have become available and have been evaluated in combination with doxorubicin, vinblastine, and dacarbazine (AVD) for the first-line treatment of patients with advanced cHL with the objective of tumor control improvement. There are still major debates with respect to first-line treatment of advanced cHL. The use of positron emission tomography-adapted strategies has allowed a reduction in the toxicity of chemotherapy regimens. Incorporation of new drugs into the treatment algorithms requires confirmation.

Vaccine strategies in the treatment of low-grade non-Hodgkin lymphoma

2008 ◽  
Vol 109 (3-5) ◽  
pp. 230-232 ◽  
Author(s):  
Anna Koumarianou ◽  
Pantelis Kountourakis ◽  
Theophanis Economopoulos
Keyword(s):  
Hodgkin Lymphoma ◽  
Low Grade ◽  
Non Hodgkin Lymphoma

Thrombotic complications in adult patients with lymphoma: a meta-analysis of 29 independent cohorts including 18 018 patients and 1149 events

Blood ◽  
2010 ◽  
Vol 115 (26) ◽  
pp. 5322-5328 ◽  
Author(s):  
Vanesa Caruso ◽  
Augusto Di Castelnuovo ◽  
Susana Meschengieser ◽  
Maria A. Lazzari ◽  
Giovanni de Gaetano ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Meta Analysis ◽  
Hematologic Malignancies ◽  
Incidence Rates ◽  
Clinical Implications ◽  
Low Grade ◽  
Thrombotic Risk ◽  
Non Hodgkin Lymphoma ◽  
Thrombotic Complications ◽  
Exact Maximum Likelihood

AbstractThrombotic complications in hematologic malignancies have important clinical implications. In this meta-analysis we sought to obtain accurate estimates of the thrombotic risk in lymphoma patients. Articles were searched in electronic databases and references. Eighteen articles were identified (29 cohorts, 18 018 patients and 1149 events). Pooled incidence rates (IRs) were calculated by the use of a method based on the exact maximum likelihood binomial distribution. The global IR of thrombosis was 6.4% (95% confidence interval [CI] 6.0%-6.8%). The global IRs of venous or arterial events were 5.3% (95% CI, 5.0%-5.7%) and 1.1% (95% CI, 0.9%-1.2%), respectively. The IR of thrombosis observed in subjects with non-Hodgkin lymphoma (NHL) was 6.5% (95% CI, 6.1%-6.9%), significantly greater than that observed for patients with Hodgkin lymphoma (4.7%; 95% CI, 3.9%-5.6%). Within NHL, patients with high-grade disease had a greater risk of events (IR 8.3%; 95% CI, 7.0%-9.9%) than low-grade disease (IR 6.3%; 95% CI, 4.5%-8.9%). This meta-analysis shows that the IR of thrombosis in lymphoma patients is quite high, especially in those with NHL at an advanced stage of the disease. These results may help better defining lymphoma populations at high thrombotic risk, to whom prophylactic approaches could be preferentially applied.

ALX148, a CD47 Blocker, in Combination with Rituximab in Patients with Non-Hodgkin Lymphoma

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-14 ◽  
Author(s):  
Tae Min Kim ◽  
Nehal Lakhani ◽  
Justin Gainor ◽  
Manali Kamdar ◽  
Philip Fanning ◽  
...  
Keyword(s):  
Immune Response ◽  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Tolerability Profile ◽  
Low Grade ◽  
Publicly Traded ◽  
Private Company ◽  
Non Hodgkin Lymphoma ◽  
Time Of Presentation

Background: CD47 is a myeloid checkpoint upregulated by tumor cells to evade the host's immune response. The high affinity CD47 blocker fusion protein, ALX148, is linked to an inactive immunoglobulin Fc region to minimize toxicity. ALX148 is half the size of an antibody, has been well tolerated, and enhances the innate and adaptive immune response against cancer in combination with anticancer therapeutics across solid and hematologic tumors (ASCO 2020 #3056, EHA 2020 #EP1247). Characterization of ALX148's tolerability profile and antitumor activity in combination with rituximab are reported in patients (pts) with non-Hodgkin Lymphoma (NHL). Methods: Patients with relapsed or refractory CD20-positive B-cell NHL for which no curative therapy was available received ALX148 (10 mg/kg QW or 15 mg/kg QW) in combination with rituximab (375 mg/m2 weekly for 4 doses followed by once monthly for 8 doses). The primary endpoint for the safety population was dose limiting toxicity (DLT). Tumor response, pharmacokinetic (PK), and pharmacodynamic (PD) markers were assessed in all pts. Data are reported as of 30Jun2020 in these fully enrolled cohorts with final data to be updated at the time of presentation. Results: A total of 33 patients with NHL were administered ALX148 in combination with rituximab. Twenty-two pts with median age of 66 years (range 32-80) were administered ALX148, 10 mg/kg QW (ALX10), in combination with rituximab [DLBCL, n=11; mantle cell lymphoma (MCL), n=4; follicular lymphoma (FL), n=5; and marginal zone lymphoma (MZL), n=2]. Eleven pts with median age of 64 years (range 53-78) were administered ALX148, 15 mg/kg QW (ALX15), in combination with rituximab (DLBCL, n=6; MCL, n=1; FL, n=3; and MZL, n=1). There have been no DLTs reported in the fully enrolled safety cohorts, and the MTD of ALX148 in combination with rituximab has not been reached. The maximum ALX148 administered dose is 15 mg/kg QW. Twenty-eight pts experienced any AE, while 16 pts reported mostly low grade treatment-related adverse events (TRAE). The most common TRAEs were rash (21%, n=7), fatigue (9%, n=3), anemia, nausea, neutropenia, and pruritus (6%, n=2 each). With a median follow up of 14 months, objective responses were observed across all histologies in response-evaluable ALX10 pts: 40.9% ORR (4CR,5PR, 6SD, n=22 total) and with a median follow up of 9 months in ALX15 pts: 63.6% ORR (3CR, 4PR, 1SD, n=11 total). Preliminary results indicate favorable ALX148 PK and near complete CD47 receptor occupancy across the dosing interval. Final results will be updated at time of presentation. Conclusions: ALX148 demonstrates excellent tolerability with durable responses in combination with rituximab in patients with relapsed/refractory NHL. The MTD of ALX148 in combination with rituximab was not reached. Encouraging preliminary activity and favorable PK/PD characteristics in combination with rituximab were observed at all dose levels with greater objective response rates reported at the MAD of 15 mg/kg QW. Disclosures Kim: Boryung: Consultancy; Voronoi: Consultancy; F. Hoffmann-La Roche Ltd/Genentech, Inc.: Consultancy; Sanofi: Consultancy; Novartis: Consultancy; Takeda: Consultancy; AstraZeneca and Korea Health Industry Development Institute: Research Funding; AstraZeneca: Consultancy. Lakhani:incyte: Research Funding; merck: Research Funding; mersana: Research Funding; northern biologics: Research Funding; odonate: Research Funding; pfizer: Research Funding; ikena: Research Funding; symphogen: Research Funding; taiRx: Research Funding; tesaro: Research Funding; livzon: Research Funding; loxo: Research Funding; macrogenics: Research Funding; inhibRx: Research Funding; cytomx: Research Funding; formation biologics: Research Funding; forty seven inc: Research Funding; alexion Pharmaceuticals: Research Funding; Alpine Biosciences: Research Funding; ALX Oncology Inc.: Research Funding; Apexian: Research Funding; asana biosciences: Research Funding; ascentage pharma: Research Funding; beigene: Research Funding; celgene: Research Funding; cerulean pharma: Research Funding; constellation pharma: Research Funding; coordination therapeutics: Research Funding; regeneron: Research Funding; sapience therapeutics: Research Funding; shattuck labs: Research Funding; innovent bio: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; jounce therapeutics: Research Funding. Gainor:theravance: Consultancy; adaptimmune: Research Funding; ariad: Research Funding; astrazeneka: Research Funding; blueprint medicines: Research Funding; lily: Consultancy; gilead sciences: Consultancy; merck: Consultancy, Research Funding; moderna therapeutics: Consultancy, Research Funding; tesaro: Research Funding; blueprint medicines: Consultancy; novartis: Research Funding; oncorus: Consultancy; regeneron: Consultancy; bristol-myers Squibb: Consultancy, Research Funding; amgen: Consultancy; array biopharma: Consultancy, Research Funding; agios: Consultancy; ironwood pharmaceuticals: Consultancy; takeda: Consultancy; genentech: Consultancy, Research Funding; jounce therapeutics: Consultancy, Research Funding. Kamdar:Roche: Research Funding. Fanning:ALX Oncology Inc.: Current Employment, Current equity holder in publicly-traded company. Squifflet:ALX Oncology Inc.: Consultancy; IDDI: Current Employment. Jin:ALX Oncology Inc.: Current Employment. Forgie:ALX Oncology Inc.: Current Employment, Current equity holder in publicly-traded company; Pfizer Inc.: Ended employment in the past 24 months. Wan:Tallac Therapeutics: Current Employment, Current equity holder in private company; ALX Oncology Inc.: Consultancy, Current equity holder in publicly-traded company. Pons:ALX Oncology Inc.: Current Employment, Current equity holder in publicly-traded company. Randolph:ALX Oncology Inc.: Current Employment, Current equity holder in publicly-traded company. Kim:F. Hoffmann-La Roche: Research Funding; Pfizer: Research Funding; JJ: Research Funding; Celltrion: Research Funding; Kyowa Kirn: Research Funding; Donga: Research Funding; Mundipharma: Research Funding.

Non-Hodgkin Lymphoma: Low Grade

2015 ◽  
pp. 614-630
Author(s):  
William Townsend ◽  
Robert Marcus
Keyword(s):  
Hodgkin Lymphoma ◽  
Low Grade ◽  
Non Hodgkin Lymphoma
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