�Hodgkin lymphoma�New options in patient management

Stephen M. Ansell, MD, PhD

Dorotha W. and Grant L. Sundquist Professor in Hematologic Malignancies Research

Chair, Division of Hematology

Mayo Clinic

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Pathology of Hodgkin Lymphoma

Courtesy of A. Feldman

Ansell et al. N Engl J Med 2015;372:311-319

Risk Factors for Early-Stage Hodgkin lymphoma

Nat Rev Clin Oncol 2012 Aug; 9(8): 450-459

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Age > 45 years

Stage IV

Male sex

White blood count > 15,000 cells/μl

Lymphocyte count < 600 cells /μl or <8%

Albumin < 4.0 g/dL

Hemoglobin < 10.5 g/dL

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Hasenclever et al. NEJM 1998; 339: 1506-1514

Prognostic Factors in Advanced Stage Hodgkin Lymphoma

Primary Therapy for Hodgkin Lymphoma

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Early stage (I and IIA) favorable disease-

2 cycles of ABVD chemotherapy plus 20 cGy involved field radiotherapy

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Early stage – interim PET negative – ABVD x 3 cycles

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Early-stage unfavorable disease –

4 cycles of ABVD chemotherapy plus 30 cGy involved field radiotherapy

Advanced disease - Combination chemotherapy –

A+AVD, A(B)VD or escalated BEACOPP (high risk patients)

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RAPID trial of PET-directed therapy for early-stage Hodgkin's lymphoma

Radford et al. N Engl J Med. 2015 Apr 23;372(17):1598-607.

PET negative –

ABVD x3 versus ABVD x3 + IFRT

Chohan KL, et al. Blood Adv. 2022 Jul 26;6(14):4241-4250.

Frontline PET-Directed Therapy with BV Plus AVD Followed By Nivolumab in Patients with Limited Stage Hodgkin Lymphoma

Park S et al. ASH 2022; #728

83 patients Limited stage cHL

97% negative interim PET scan

2 patients came off study and got RT

100% remained progression free after nivolumab consolidation

Nivolumab and AVD in Early-Stage Unfavorable Hodgkin Lymphoma: GHSG Nivahl Trial

• 109 patients aged 18-60 years with early-stage unfavorable HL.
• Patients received concomitant (4xnivo-AVD; arm A) or sequential (4xnivolumab, 2xnivo-AVD, 2xAVD; arm B) treatment
• Each followed by 30Gy involved-site radiotherapy (IS-RT).

Bröckelmann et al. J Clin Oncol. 2023 Feb 20;41(6):1193-1199. 

Brentuximab Vedotin, Nivolumab, Doxorubicin, and Dacarbazine (AN+AD) for Early-Stage Classical Hodgkin Lymphoma

Abramson et al. ASH 2023, abstract 611

Treatment Guided by PET in Advanced Hodgkin Lymphoma: RATHL Trial

Johnson et al. N Engl J Med. 2016 Jun 23;374(25):2419-29.

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If you start with ABVD, you can drop the bleomycin if PET-2 negative

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Not clear that escalating therapy in PET-2 patients improves outcome

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Luminari et al. ASH 2022; #315

PET-2 negative

PET-2 positive

Ansell SM et al. N Engl J Med. 2022 Jul 28;387(4):310-320.

Outcomes with Brentuximab Vedotin + AVD vs. ABVD in Stage III or IV Hodgkin's Lymphoma

PFS

Overall Survival

BrECADD Proves Non-inferior to eBEACOPP in Advanced Classical Hodgkin Lymphoma (HD21 trial)

BrECADD - brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone

1500 patients, 749 were randomly assigned to eBEACOPP and 751 were assigned to BrECADD. 

At a median follow-up of 40 months, the estimated 3-year PFS rate with BrECADD (n = 740) was 94.9% (99% CI, 92.8%-97.1%) vs 92.3% (99% CI, 89.7%-94.9%) with eBEACOPP (n = 742) in the intention-to-treat (ITT) population (HR, 0.63; 99% CI, 0.37-1.07).

The 1-year PFS rate with BrECADD was 97.5% (99% CI, 96%-99%).

The estimated 3-year OS rate was 98.5% in both the BrECADD and eBEACOPP arms

Borchmann P, et al. Hematol Oncol. 2023;41(suppl 2):881-882. doi:10.1002/hon.3196_LBA5

Nivolumab+AVD for Newly Diagnosed Advanced-Stage cHL

Herrera et al. J Clin Oncol 41, 2023 (suppl 17; abstr LBA4).

Nivolumab-AVD Is Better Tolerated and Improves PFS Compared to Bv-AVD in Older Patients (Aged ≥60 Years) with Advanced Stage Hodgkin Lymphoma

Rutherford et al. ASH 2023, abstract 181

Castellino et al. ASH 2023, abstract 610

PFS and Toxicity with Nivolumab-AVD Compared to BV-AVD in Pediatric Advanced Stage cHL, Results of SWOG S1826

Brentuximab Vedotin, Nivolumab, Doxorubicin, and Dacarbazine for Advanced Stage Classical Hodgkin Lymphoma

Lee et al. ASH 2023, abstract 608

Moskowitz et al. J Clin Oncol. 2021 Oct 1;39(28):3109-3117.

Pembrolizumab Plus GVD As Second-Line Therapy for Relapsed or Refractory cHL

• 39 patients enrolled, 41% had refractory disease and 38% relapsed within 1 year of frontline treatment. 
• ORR and CR rates after pembro-GVD were 100% and 95%, respectively.
• 36 (95%) patients proceeded to ASCT, 13 (33%) received post-ASCT brentuximab vedotin maintenance.
• All 36 transplanted patients were in remission at a median post-transplant follow-up of 13.5 months.

Nivolumab Plus ICE As First Salvage Therapy in High-Risk Relapsed/Refractory Hodgkin Lymphoma

Mei et al. Blood. 2022 Jun 23;139(25):3605-3616.

• After nivolumab, the ORR was 81%, and the CR rate was 71%.
• At the end of protocol therapy, the ORR and CR rates were 93% and 91%.
• Thirty-three patients were bridged directly to AHCT, including 26 after Nivo alone.

• The 2-year PFS and OS were 72% and 95%, respectively. 

Desai et al. ASH 2023, abstract 182

PD-1 Blockade before Autologous Stem Cell Transplantation Improves Outcomes in Relapsed/Refractory cHL

Relapse post transplant - CD30 directed CAR T-cells are promising

Ramos et al. J Clin Oncol. 2020 Nov 10;38(32):3794-3804.

Favezelimab (anti–LAG-3) Plus Pembrolizumab in R/R Classical Hodgkin Lymphoma after Anti–PD-1 Treatment

34 patients

10 pts had objective response (ORR, 29%; CR 3 [9%]; PR 7 [21%]).

Median PFS was 9.7 months

Timmerman et al. ASH 2023; #4440

42 patients

ORR and CR were 92.8% and 66.7%, respectively (94.4% and 72.2%, respectively, in 36 pts treated at the RP2D). Nine pts had a response consolidated with SCT (5 allo, 4 auto).

At median follow-up of 14 (6-34) months, the EFS/OS rates are 31%/76%

AFM13 Combined with Preactivated and Expanded Cord Blood-Derived NK Cells for R/R CD30+ Lymphoma

Nieto et al. ASH 2023; #774

New options for classical Hodgkin lymphoma patients

1. To include new agents (particularly PD-1 blockade) in initial therapy
2. To add PD-1 antibodies to salvage therapy prior to autologous stem cell transplantation
3. To consider clinical trials testing novel agents for patients relapsing post transplant

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