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. 2023 Dec 15;153(12):2019-2031.
doi: 10.1002/ijc.34693. Epub 2023 Aug 21.

Stage 4N neuroblastoma before and during the era of anti-GD2 immunotherapy

Brian H Kushner  1 , Michael P LaQuaglia  2 , Fiorella Iglesias Cardenas  1 , Ellen M Basu  1 , Justin T Gerstle  2 , Kim Kramer  1 , Stephen S Roberts  1 , Suzanne L Wolden  3 , Nai-Kong V Cheung  1 , Shakeel Modak  1
Affiliations

Stage 4N neuroblastoma before and during the era of anti-GD2 immunotherapy

Brian H Kushner et al. Int J Cancer. .

Abstract

Patients with stage 4N neuroblastoma (distant metastases limited to lymph nodes) stand out as virtually the only survivors of high-risk neuroblastoma (HR-NB) before myeloablative therapy (MAT) and immunotherapy with anti-GD2 monoclonal antibodies (mAbs) became standard. Because no report presents more recent results with 4N, we analyzed our large 4N experience. All 51 pediatric 4N patients (<18 years old) diagnosed 1985 to 2021 were reviewed. HR-NB included MYCN-nonamplified 4N diagnosed at age ≥18 months and MYCN-amplified 4N. Among 34 MYCN-nonamplified high-risk patients, 20 are relapse-free 1.5+ to 37.5+ (median 12.5+) years post-diagnosis, including 13 without prior MAT and 5 treated with little (1 cycle; n = 2) or no mAb (n = 3), while 14 patients (7 post-MAT, 8 post-mAbs) relapsed (all soft tissue). Of 15 MYCN-amplified 4N patients, 7 are relapse-free 2.1+ to 26.4+ (median 11.6+) years from the start of chemotherapy (all received mAbs; 3 underwent MAT) and 4 are in second remission 4.2+ to 21.8+ years postrelapse (all soft tissue). Statistical analyses showed no significant association of survival with either MAT or mAbs for MYCN-nonamplified HR-NB; small numbers prevented these analyses for MYCN-amplified patients. The two patients with intermediate-risk 4N (14-months-old) are relapse-free 7+ years postresection of primary tumors; distant disease spontaneously regressed. The natural history of 4N is marked by NB confined to soft tissue without early relapse in bones or bone marrow, where mAbs have proven efficacy. These findings plus curability without MAT, as seen elsewhere and at our center, support consideration of treatment reduction for MYCN-nonamplified 4N.

Keywords: immunotherapy; metastases; neuroblastoma; prognosis; radiotherapy.

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Conflict of interest statement

Conflict of Interest: BHK, MPL, FI-C, EMB, SSR, and SLW declare no potential conflicts of interest. JTG has financial stock/shares in Pfizer, Merck, and Bristol Myers Squibb. SM is a consultant to Y-mAbs Therapeutics Inc, Kymera, US WorldMeds, EUSA, and Inervate. KK is a consultant/equity holder in Y-mAbs Therapeutics Inc. NKC reports receiving past commercial research grants from Y-mAbs Therapeutics and Abpro-Labs Inc.; holding ownership interest/equity in Y-mAbs Therapeutics Inc., and Abpro-Labs, and owning stock options in Eureka Therapeutics. NKC is the inventor and owner of issued patents licensed by Memorial Sloan Kettering Cancer Center (MSK) to Y-mAbs Therapeutics Inc., Biotec Pharmacon, and Abpro-Labs Inc. Hu3F8, 8H9, huHIM3-4, huA33, SADA-R and GD2/GD3 vaccine were licensed by MSK to Y-mAbs Therapeutics Inc. Both MSK and NKC have financial interest in Y-mAbs Therapeutics Inc.

Figures

Figure 1.
Figure 1.
Kaplan-Meyer analysis of progression-free (A) and overall (B) survival of 34 patients with high-risk MYCN-non-amplified stage 4N neuroblastoma treated at Memorial Sloan Kettering Cancer Center (1985-2021).
See this image and copyright information in PMC

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