Novel drugs and strategies around ASCT for Hodgkin lymphoma

In recent years, several developments have resulted in improved outcomes for patients with primary refractory or relapsed classic Hodgkin lymphoma (cHL) who are eligible for autologous stem cell transplantation (ASCT), including the introduction of new drugs in combination with salvage chemotherapy before ASCT, and improved consolidation strategies after ASCT. Dr Anna Sureda (Catalan Institute of Oncology, Spain) discussed the latest updates in the field [1].

ASCT is the standard-of-care for patients with classical cHL who achieve a second complete remission, being primary refractory or having relapsed after a first line of therapy [2]. “It appears that we are autografting fewer patients in recent years, due to improved first-line therapies,” stated Dr Sureda.

For example, the ECHELON-1 trial showed that the experimental regimen of brentuximab vedotin plus AVD chemotherapy outperformed ABVD in terms of modified progression-free survival (PFS) and overall survival (OS) in patients with stage III or IV cHL [3,4]. Another emerging option is to combine AVD chemotherapy with checkpoint inhibitors such as pembrolizumab, which appears to be beneficial for patients with untreated cHL [5].

“Despite these encouraging developments, we still see a population of predominantly young patients that need ASCT,” noted Dr Sureda. A trial by Schmitz et al. showed that ASCT is the standard-of-care for patients with relapsed or primary refractory cHL [6]. However, this trial also displayed that approximately 50% relapsed after ASCT. “Can we improve the results of ASCT in patients with primary refractory or relapsed cHL?” asked Dr Sureda.

Improving the outcomes of ASCT

“We have used 2 strategies to improve the outcomes of ASCT,” said Dr Sureda. The first strategy is to differentiate patients with respect to the expected disease response using imaging techniques, such as PET or metabolic tumour volume (MTV) assessments, prior to ASCT [7,8]. The second strategy is incorporating drugs in the salvage setting before ASCT, such as brentuximab vedotin, targeting CD30-positive cells, or the checkpoint inhibitors nivolumab and pembrolizumab [9–11].

Several phase 1 and 2 trials assessing the combination of brentuximab vedotin and salvage chemotherapy before ASCT have indicated that this strategy leads to excellent outcomes (see Figure). The benefit appears to be more pronounced in relapsed patients compared with primary refractory patients [12]. “Whether brentuximab vedotin plus chemotherapy is superior to chemotherapy alone in the second line setting has not yet been demonstrated,” said Dr Sureda.

Figure: Outcomes of brentuximab vedotin plus salvage chemotherapy before ASCT [1]



Next, chemotherapy plus pembrolizumab resulted in an overall response rate of 100% and a complete response rate of 95% in 38 patients who were treated with this regimen in the second line, before ASCT [13]. After a median follow-up of 30 months, the progression-free survival was 96%. Also, Advani et al. showed that chemotherapy-free regimens may lead to good outcomes in the second-line treatment for patients with cHL [14].

Is consolidation with ASCT always needed?

“Another question I would like to address is: Do we need to consolidate all patients with ASCT?” Dr Sureda continued. “We do not have the answer at this point.” However, clinical trials are investigating this issue. Patients with primary refractory or relapsed cHL in the phase 2b BRESELIBET trial (NCT04378647) received either chemotherapy plus brentuximab vedotin or chemotherapy alone. Patients that achieved a metabolic complete response (n=22) were not consolidated with ASCT but with brentuximab vedotin. Similarly, in the trial by Moskowitz et al., patients who reached a complete remission on chemotherapy plus pembrolizumab were consolidated with pembrolizumab instead of an ASCT [13]. “Data from these trials may give us some insights into this issue,” added Dr Sureda.

The role of consolidation after ASCT

“We also know that some patients are more likely to relapse after ASCT than others,” continued Dr Sureda. To decrease the relapse rate after ASCT, the phase 3 AETHERA trial randomised 329 high-risk patients who had received ASCT 1:1 to brentuximab vedotin consolidation therapy or to placebo [15]. The trial was positive, with a 43% reduction in the risk of relapse or progression for patients in the experimental arm compared with patients in the control arm. The long-term outcomes of this trial confirmed that consolidation with brentuximab vedotin after ASCT leads to better outcomes than placebo in high-risk patients [16]. “Emerging data showed that pembrolizumab may be a promising agent for consolidation after ASCT as well,” added Dr Sudera [17]. Finally, the combination of brentuximab vedotin and nivolumab, as a consolidation strategy after ASCT, displayed an encouraging progression-free survival rate of 92% after 19 months of follow-up in a group of high-risk patients (n=59) [18].

“With these encouraging developments going on, hopefully, we will be able to find a subset of patients with cHL in whom we can omit consolidation with ASCT in the nearby future,” Dr Sureda concluded her talk.

1. Sureda A. Hodgkin’s lymphoma. State of the art of autologous stem cell transplantation. E10-02, European Society for Blood and Marrow Transplantation (EBMT) 49^th Annual Meeting, 23–26 April 2023, Paris, France.
2. Snowden J, et al. BMT. 2022;57(8):1217–1239.
3. Straus DJ, et al. Blood. 2020;135(10):735–742.
4. Ansell SM, et al. Abstract 7503, ASCO 2022, 03–07 June, Chacago, USA.
5. Lynch RC, et al. Blood. Doi:10.1182/blood.2022019254.
6. Schmitz N, et al. Lancet. 2002;359(9323):2065–2071.
7. Moskowitz CH, et al. Blood. 2012;119(7):1665–1670.
8. Moskowitz AJ, et al. Blood. 2017;130(20):2196–2203.
9. Gopal AK, et al. Blood. 2015;125(8):1236–1243.
10. Ansell S, et al. ICML. 2021;21(1):S373–S374.
11. Armand P, et al. Blood. 2021;138(1):1366.
12. Driessen J, et al. Abstract 876, ASH 2021, 11–14 December, Atlanta, USA.
13. Moskowitz AJ, et al. JCO. 2021;39(28):3109–3117.
14. Advani RH, et al. Blood. 2021;138(6):427–438.
15. Moskowitz CH, et al. Lancet. 2015;385(9980):1853–1862.
16. Moskowitz CH, et al. Blood. 2018;132(25):2639–2642.
17. Armand P, et al. Blood. 2019;134(1):22–29.
18. Herrera AF, et al. Abstract 472, ASH 2020, 05–08 December.

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Posted on 15 June, 202318 March, 2024