Atabani, Suha

Bloor, Adrian

Gibb, Adam

Illidge, Timothy

Kulkarni, Samar

Linton, Kim

Murray, John

Piddock, Katherine

Radford, John

English

Abstract: Brentuximab vedotin (BV), a CD30 targeted antibody drug conjugate, has demonstrated impressive activity inboth Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) in phase II studies. Real world experience in anumber of named patient programmes (NPP) have been reported but few long-term outcomes have been described.Here we describe clinical outcomes for a group of 33 patients (pts) that received BV via a NPP or following conditionallicensing by the European Medicines Agency. We update previously reported outcomes for 24 pts (Gibb et al,Haematologica 2013) with more than 3 years additional follow-up and 9 new pts.Thirty-three pts with CD30+ T-cell lymphoma who were relapsed or refractory after previous chemotherapy or autotransplant,had a positive PET-CT scan and deemed suitable for systemic therapy were treated. Response was assessedusing PET-CT after 4 (PET4) and 8 cycles (PET8). Of the 33 pts included, 18 (55%) were female with median age(range) of 40 years (21-77). Twenty-four pts had HL, 8 ALCL and 1 angio-immunoblastic T-cell lymphoma. The median(range) number of prior systemic therapies was 2 (1-5) of which 15 had prior radiotherapy and 9 had received anautotranplant.Pts received a median of 5 cycles of BV (range 1-16) at a dose of 1.8mg/kg once every 3 weeks. The overall responserate (ORR) was 61%. By histology the ORR was 63% in both HL (15/24) and ALCL (5/8), and 0% in angioimmunoblasticT-cell lymphoma (AITL) (0/1). Complete response rate was 24% (HL n=4, ALCL n=4); this was higher in the ALCL group(50%, 4/8) than the HL group (17%, 4/24). Overall, the best response was seen at PET4 in all but 1 pt with HL whoimproved to CR at PET8.Of the 25 pts who were eligible for allotransplant (allo-T), 8 (32%) proceeded to allo-T without further systemic therapy.Median number of cycles of BV received prior to allo-T was 6 (range 5-8). Responses to BV were either CR (n=5) or PR(n=3), 2 of whom received consolidation radiotherapy. Seven pts were assessed for toxicity and outcomes following allo-T (n=1 lost to follow-up after transferring to another centre). After a median follow-up of 25.3 months (range 2.4 - 59.8) 5pts are still alive. Acute graft versus host disease (GvHD) was seen in 5 pts (71%); this involved the skin (grade 1-2,n=5), gut (grade 2-3, n=3) or liver (grade 1, n=1). Chronic GvHD was seen in 3 pts (43%). Two pts had overlapsyndrome. Six pts experienced bacterial and viral infections that were successfully treated in all but 1 pt. One further ptdied following severe GvHD.Of the pts that did not receive an allo-T, 14 had an inadequate response (PD at PET4 n=3, PD at PET8 n=7, PD or deathbefore PET4 n=3, SD n=1). A further 3 pts declined allo-T, 2 of these had achieved CR and remain alive (1 progressionfree)at 23.0 and 56.1 months of follow-up. Four pts proceeded to allo-T after additional systemic therapy.In pts with relapsed/refractory CD30+ve lymphoma treated with BV outside a clinical trial protocol we have shown thatresponse rates and toxicity are broadly comparable with the published phase II trial data. Best long term outcomes wereseen in pts that achieved CR and/or underwent allotransplant with 6 pts in this category (18% of entire cohort) alive anddisease-free up to 5 years later. We conclude that prolonged survival is possible after BV in a proportion of real world ptswhose prognosis is conventionally regarded as extremely poor

The University of Manchester - Institutional Repository

The University of Manchester ResearchReal World Experience With Brentuximab Vedotin inRelapsed/Refractory CD30 Positive LymphomaDocument VersionOther versionLink to publication record in Manchester Research ExplorerCitation for published version (APA):Piddock, K., Atabani, S., Gibb, A., Bloor, A., Murray, J., Kulkarni, S., Illidge, T., Linton, K., & Radford, J. (2017).Real World Experience With Brentuximab Vedotin in Relapsed/Refractory CD30 Positive Lymphoma: Outcomes in33 Patients After Prolonged Follow-up At a Single UK Centre.Citing this paperPlease note that where the full-text provided on Manchester Research Explorer is the Author Accepted Manuscriptor Proof version this may differ from the final Published version. If citing, it is advised that you check and use thepublisher's definitive version.General rightsCopyright and moral rights for the publications made accessible in the Research Explorer are retained by theauthors and/or other copyright owners and it is a condition of accessing publications that users recognise andabide by the legal requirements associated with these rights.Takedown policyIf you believe that this document breaches copyright please refer to the University of Manchester’s TakedownProcedures [http://man.ac.uk/04Y6Bo] or contact uml.scholarlycommunications@manchester.ac.uk providingrelevant details, so we can investigate your claim.Download date:09. Jun. 2022BSH AbstractsLymphoma/CLLBSH2017-207Real World Experience With Brentuximab Vedotin in Relapsed/Refractory CD30 Positive Lymphoma: Outcomes in33 Patients After Prolonged Follow-up At a Single UK CentreKatherine Piddock* 1, Suha Atabani1, Adam Gibb1, Adrian Bloor1, John Murray1, Samar  Kulkarni1, Tim Illidge1, Kim Linton1, 2, John Radford1, 21The Christie NHS Foundation Trust, 2Manchester Academic and Health Science Centre, University of Manchester,Manchester, United KingdomPresentation Method: Oral or posterHas this abstract been presented at a British meeting previously?: NoHas the abstract been presented at an overseas meeting?: NoSpeciality: Clinical ScientistAbstract: Brentuximab vedotin (BV), a CD30 targeted antibody drug conjugate, has demonstrated impressive activity inboth Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) in phase II studies. Real world experience in anumber of named patient programmes (NPP) have been reported but few long-term outcomes have been described.Here we describe clinical outcomes for a group of 33 patients (pts) that received BV via a NPP or following conditionallicensing by the European Medicines Agency. We update previously reported outcomes for 24 pts (Gibb et al,Haematologica 2013) with more than 3 years additional follow-up and 9 new pts.Thirty-three  pts  with  CD30+  T-cell  lymphoma  who  were  relapsed  or  refractory  after  previous  chemotherapy  or  auto-transplant, had a positive PET-CT scan and deemed suitable for systemic therapy were treated. Response was assessedusing  PET-CT  after  4  (PET4)  and  8  cycles  (PET8).  Of  the  33  pts  included,  18  (55%)  were  female  with  median  age(range) of  40 years (21-77).  Twenty-four pts had HL, 8 ALCL and 1 angio-immunoblastic T-cell  lymphoma. The median(range)  number  of  prior  systemic  therapies  was  2  (1-5)  of  which  15  had  prior  radiotherapy  and  9  had  received  anautotranplant.Pts received a median of 5 cycles of BV (range 1-16) at a dose of 1.8mg/kg once every 3 weeks. The overall responserate (ORR) was 61%. By histology the ORR was 63% in both HL (15/24) and ALCL (5/8), and 0% in angioimmunoblasticT-cell lymphoma (AITL) (0/1). Complete response rate was 24% (HL n=4, ALCL n=4); this was higher in the ALCL group(50%,  4/8)  than  the  HL  group  (17%,  4/24).  Overall,  the  best  response  was  seen  at  PET4  in  all  but  1  pt  with  HL  whoimproved to CR at PET8.Of the 25 pts who were eligible for  allotransplant  (allo-T),  8 (32%) proceeded to allo-T without  further systemic therapy.Median number of cycles of BV received prior to allo-T was 6 (range 5-8). Responses to BV were either CR (n=5) or PR(n=3), 2 of whom received consolidation radiotherapy. Seven pts were assessed for toxicity and outcomes following allo-T (n=1 lost to follow-up after transferring to another centre). After a median follow-up of 25.3 months (range 2.4 - 59.8) 5pts  are  still  alive.  Acute  graft  versus  host  disease  (GvHD)  was  seen  in  5  pts  (71%);  this  involved  the  skin  (grade  1-2,n=5),  gut  (grade  2-3,  n=3)  or  liver  (grade  1,  n=1).  Chronic  GvHD  was  seen  in  3  pts  (43%).  Two  pts  had  overlapsyndrome. Six pts experienced bacterial  and viral infections that were successfully treated in all  but 1 pt.  One further ptdied following severe GvHD.Of the pts that did not receive an allo-T, 14 had an inadequate response (PD at PET4 n=3, PD at PET8 n=7, PD or deathbefore PET4 n=3, SD n=1). A further 3 pts declined allo-T, 2 of these had achieved CR and remain alive (1 progression-free) at 23.0 and 56.1 months of follow-up. Four pts proceeded to allo-T after additional systemic therapy.In pts with relapsed/refractory CD30+ve lymphoma treated with BV outside a clinical trial protocol we have shown thatresponse rates and toxicity are broadly comparable with the published phase II trial data. Best long term outcomes wereseen in pts that achieved CR and/or underwent allotransplant with 6 pts in this category (18% of entire cohort) alive anddisease-free up to 5 years later. We conclude that prolonged survival is possible after BV in a proportion of real world ptswhose prognosis is conventionally regarded as extremely poor. Disclosure of Interest: K. Piddock: None Declared, S. Atabani: None Declared, A. Gibb Conflict with: Educationalsupport and Advisory board/lecture fees from Takeda, A. Bloor: None Declared, J. Murray: None Declared, S. Kulkarni:None Declared, T. Illidge Conflict with: Speakers bureau and consultancy Takeda, K. Linton Conflict with: Takeda, J.Radford Conflict with: Takeda,  Conflict with: Honoraria from Takeda, Seattle Genetics and Novartis. Shareholdings inGlaxoSmithKline and AstraZeneca (spouse)Keywords: lymphoma, Real-world management, relapsed and refractory lymphoma

Real World Experience With Brentuximab Vedotin in Relapsed/Refractory CD30 Positive Lymphoma:Outcomes in 33 Patients After Prolonged Follow-up At a Single UK Centre

https://pure.manchester.ac.uk/ws/files/68288629/Piddock_BSH2017_207_preview_4.pdf

Real World Experience With Brentuximab Vedotin in Relapsed/Refractory CD30 Positive Lymphoma:Outcomes in 33 Patients After Prolonged Follow-up At a Single UK Centre

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