Verbutuximab adds another indication!

Introduction The good news of lymphoma treatment continues, and the antibody-conjugated drug Vibutuximab has added new indications in China [1].

A few days ago, Verbutuximab (BV) for injection was approved by the National Medical Products Administration (NMPA) for the treatment of CD30-positive primary cutaneous anaplastic large cell lymphoma (pcALCL) that has received systemic treatment in the past.
Or adult patients with mycosis fungoides (MF).

This is a newly added indication after BV was approved in China last year for CD30-positive relapsed or refractory systemic anaplastic large cell lymphoma (sALCL) and classic Hodgkin lymphoma (cHL) adult patients .

The new indications of BV, pcALCL and MF, belong to cutaneous T-cell lymphoma (CTCL), and CTCL belongs to peripheral T-cell lymphoma disease.

CTCL is a group of heterogeneous extranodal non-Hodgkin's lymphomas originating from skin T cells, which are mainly confined to the skin at the time of diagnosis (Figure 1).

In CTCL, MF is the most common subtype (accounting for 50% to 70% of CTCL), and primary skin CD30-positive lymphoproliferative disease is the second largest subtype (including pcALCL and lymphomatoid papulosis) [ 2-6].

Figure 1 Tumor stage MF (top) and pcALCL (bottom) [8,9] At present, systemic treatments for CTCL rarely provide reliable and long-lasting remission, and most single-agent treatments have an objective remission rate of 20% to 35%.
The duration of remission is 4 to 6 months; the efficacy of multi-drug chemotherapy is not satisfactory, and remission usually only lasts for 3 to 6 months [7].

CD30 is highly expressed in CTCL subtypes, especially MF and pcALCL [7], which provides a reliable target for treatment.

The approval of the CD30-targeting antibody-conjugated drug BV in two subtypes of CTCL has brought new treatment options and hopes for the treatment of lymphoma in China! The ALCANZA study provides strong evidence for the approval of the new BV indication.
The approval of the new BV indication is mainly based on the data of the ALCANZA study.

The ALCANZA study is an international, multi-center, randomized, open-label Phase III trial, carried out in 52 medical centers in 13 countries/regions around the world, to evaluate the use of new drugs BV and traditional therapies in patients with CD30-positive CTCL The efficacy and safety of [7].

The study included previously treated adult patients with CD30 positive MF (previously received ≥1 system therapy) or pcALCL (previously received ≥1 system therapy or radiotherapy) and were randomly assigned (1:1) to give BV (1.
8 mg/ kg, intravenous injection, once every 3 weeks, up to 16 cycles) or the treatment plan chosen by the doctor (methotrexate 5-50 mg, orally, once a week, up to 48 weeks; or bexarotene 300 mg /m2 (target dose), orally, once a day, up to 48 weeks), until the disease progresses or the toxicity becomes intolerable.

The primary endpoint was the proportion of patients who achieved objective remission and lasted ≥ 4 months (ORR4).

The key secondary endpoints are complete remission (CR) rate, progression-free survival (PFS), and symptom burden (assessed by the health-related quality of life measurement tool Skindex-29).

The results showed that a total of 131 patients were enrolled (66 in the BV group and 65 in the treatment group selected by the doctor), of which 128 were included in the intention-to-treat population (64 in each of the two treatment groups).

Except for the more cases of stage IVB MF and extradermal pcALCL in the BV group, the baseline characteristics of the two treatment groups were basically balanced.

01 Primary endpoint ORR4: BV was significantly better than the doctor's choice of treatment plan.
The median follow-up was 22.
9 months.
The ORR4 of the BV group was significantly better than the doctor's choice of treatment group (56.
3% vs 12.
5%), with a difference of 43.
8% (95% CI 29.
1) -58.
4; P<0.
0001); In different disease and state subgroups, BV treatment also has an ORR4 advantage (Figure 2). Figure 2 Proportion of patients who achieved objective remission for at least 4 months 02 Key secondary endpoints CR rate, PFS, symptom burden: BV group is better than doctors choose treatment group Compared with doctors choose treatment group, the CR rate of BV group is significantly higher (16% vs 2%; P=0.
0046), the median PFS (according to the EMA standard) was significantly longer (16.
7 months vs 3.
5 months; Figure 3), and patients reported a greater degree of symptom burden reduction (Skindex-29 The mean maximum decrease in symptom-related scores compared to baseline: -27.
96 vs -8.
62; P<0.
0001).

Figure 3 In terms of the safety of patients with progression-free survival, the incidence of serious adverse events (AE) was similar in the two groups (both 29%).

No new or unexpected toxicity occurred in BV treatment.

The incidence of peripheral neuropathy (PN) in the BV group was higher than that in the treatment group selected by the physician [67% (44/66) vs 6% (4/62)], but at the last follow-up (median 22.
9 months), BV In the group, 82% (36/44) of the PN symptoms were improved (≥ grade 1) or subsided.

03 Research Value and Significance The ALCANZA study is the first randomized study comparing new drugs with traditional therapies for the treatment of CTCL, and it is also the largest phase III clinical study carried out in CTCL patients.

Unlike many studies, this study used the current international consensus efficacy standards (including skin, lymph node, internal organs and blood efficacy) for efficacy evaluation.

In addition, this study showed for the first time in a phase III trial that a new drug treatment of CTCL has a significant benefit over traditional therapies: Compared with the doctor’s choice of methotrexate or bexarotene, BV can significantly improve ORR4, increase CR rate, and prolong PFS , To reduce the burden of symptoms reported by patients.

Concluding remarks Less than a year after BV's first domestic indication was approved, it has added new indications, which shows that innovative tumor drugs are "accelerating.
"
The good news of lymphoma treatment continues, and patients will rekindle their hopes and get greater benefits! References[1] Am J Hematol 2016;91:152-165.
[3]BekkenkMW, et al.
Blood 2000;95:3653-61.
[4]BradfordPT, et al.
Blood 2009;113:5064-73.
[5]CriscioneVD, and Weinstock MA.
Arch Dermatol.
2007;143:854-859.
[6 ]WillemzeR, Jaffe ES, Burg G et al.
Blood2005;105:3768-3785.
[7]Prince HM, Kim YH, HorwitzSM, et al.
Brentuximab vedotin or physician's choice in CD30-positive cutaneousT-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial[J].
Lancet.
2017;390(10094):555-566.
[8]CeciliaLarocca,et al.
Hematol Oncol Clin North Am.
2019 February; 33( 1): 103–120.
[9] Kamil Abed,etal.
Medicine (2018) 97:4 Statement This information is intended to help medical and health professionals better understand the latest developments in the field of related diseases.

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