A Latin-American Cancer Center Experience in the Treatment of Hodgkin's Lymphoma during a Drug Shortage
Authors: Rubalcava Luis Felipe Felipe , Cesarman-Maus Gabriela , Ramirez-Ibarguen Ana Florencia 
Published: November 2021

Abstract
The treatment of Hodgkin's lymphoma has been characterized by a story of success with the use tried-and-true protocols. During the second half of 2019 to the first-half of the 2021 the Mexican health system experienced a shortage of drugs, which compromised the possibility of using in most of the common protocols for this cancer: ABVD, BEACOPP, IGEV, ESHAP, DHAP, GEMOX. Clinician had option of using a common protocol with incomplete doses or applying an alternative complete CHOEP protocol, which has been used with some success in exploratory studies [1,2]. For 12 months, we treated a total of 58 patients of which we compared the base characteristics and response rates to 10-year compiled data from pre-shortage patients (PS) (total 475).
The baseline characteristics of the PS vs shortage (S) group showed a statistical similar gender distribution (males 55.2% vs 63.8%, P 0.21), histologic subtype (P 0.24), international prognostic score (IPS ≥3 57.7% vs 58.6%, P 0.89) and clinical stage (advanced 78.1% vs 84.5%, P 0.26). The S patients did show higher frequency of B symptoms (P 0.002), extranodal disease (P 0.0001), while the PS group had a higher frequency of bulky disease (P 0.001), ABVD protocol (96% vs 63.8%, P 0.0001) and radiotherapy use.
In the S group a total of 37 ABVD (29 incomplete), 7 BEACOPP (5 incomplete) and 14 CHOEP protocols (1 incomplete) were infused, it means only 10 (17.7%) were able to receive a standard complete treatment, while the rest received an incomplete or alternative treatment. Complete response for the PS and S group were 71.4% vs 56.9% with the corresponding therapeutic failure 28.6% vs 43.1% (p 0.023) respectively. Analyzing the response rate of each chemotherapy protocol in the S group, the complete ABVD vs incomplete ABVD demonstrated an 87.5% vs 69% (p 0.28) respectively. The complete BEACOPP vs incomplete showed 50% vs 40% (p 0.7) and CHOEP exhibited an unexceptional complete response rate of 21.4%.
The median follow up was 48 months (1-148) for all cohort. One year OS were 98% vs 82% on PS vs S group respectively (log rank 0.0001). One year-PFS for the PS and S group were 96% and 61% respectively (log rank 0.003).
The risk factors associated with lower PFS were B symptoms (OR 1.7, 1.1-2.6), advanced disease (OR 1.66, 1-0-2.7) and IPS≥3 (OR 2.1, 1.4-3.3); as favorable factors we observed radiotherapy (OR 0.07, 0.6-0.8) and the PS group (OR 0.5, 0.3-1.0); however, in the Cox regression, only the IPS≥3 remained as an independent unfavorable factor (HR 1.8, 1.2-2.6), as did radiotherapy (HR 0.4, 0.3-0.6) as favorable. For the OS the drug shortage were an independent risk factor (HR 2.2, 1.1-4.3) like IPS ≥3 (HR 2.8, 1.5-5.1). Analyzing the 1-year PFS in the S group according to which chemotherapy protocol they received, those with ABVD or BEACOPP (regardless of the complete dose status) was of 72%, compared to 20% (P 0.001) in the CHOEP regimen.
CHOEP regimen in LH patients is ineffective treatment. In times of shortages, continuing with incomplete standard schemes offers better response rates than alternative schemes. Despite Hodgkin's lymphoma is considered a neoplasm with high cure rates when an economic recession followed by an international event (for example a global pandemic) limited our availability for the use of standard treatments, an area of opportunity for considering alternative protocols has risen for resource-limited countries and institutions.
[1] Walewski J,et al. CHOP-21 for unfavorable Hodgkin's lymphoma. An exploratory study. Med Oncol. 2010;27(2):262-7
[2] Kolstad A, et al. Standard CHOP-21 as first line therapy for elderly patients with Hodgkin's lymphoma. Leuk Lymphoma. 2007;48(3):570-6

Disclosures
No relevant conflicts of interest to declare.