Blinatumomab for First-Line Treatment of Children and Young Persons With B-ALL

Abstract

PURPOSE We tested whether blinatumomab (Blina) is effective as a toxicity-sparing alternative to first-line intensive chemotherapy in children and young persons (CYP) with B-ALL who were chemotherapy-intolerant or chemotherapy-resistant. METHODS Data were collected for consecutive CYP (age 1-24 years) with Philadelphia chromosome–positive or Philadelphia chromosome–negative B-ALL who received Blina as first-line therapy. Blina was given as replacement for postremission intensive chemotherapy to patients with chemotherapy intolerance or resistance. Blina responders received further chemotherapy (Blin-CT) or first remission hematopoietic stem-cell transplant (Blin-HSCT) if indicated. Event-free survival (EFS) and overall survival (OS) of the Blin-CT group were compared with those of matched controls treated with standard chemotherapy in the UKALL 2003 trial. Events were defined as death, relapse, or secondary cancer. RESULTS From February 2018 to February 2023, 105 patients were treated, of whom 85 were in the Blin-CT group and 20 were in the Blin-HSCT group. A majority of Blin-CT patients received Blina for chemotherapy intolerance (70 of 85, 82%), and the group had a higher-risk profile than unselected patients with B-ALL. Blina was well tolerated with only one patient having a grade 3/4–related toxicity event, and of the 60 patients who were minimal residual disease–positive pre-Blina, 58 of 60 (97%) responded. At a median follow-up of 22 months, the 2-year outcomes of the 80 matched Blin-CT group patients were similar to those of 192 controls (EFS, 95% [95% CI, 85 to 98] v 90% [95% CI, 65 to 93] and OS, 97% [95% CI, 86 to 99] v 94% [95% CI, 89 to 96]). Of the 20 in the HSCT group, three died because of transplant complications and two relapsed. CONCLUSION Blina is safe and effective in first-line treatment of chemotherapy-intolerant CYP with ALL.

Bispecific monoclonal antibody blinatumomab in the first-line therapy of B-lineage acute lymphoblastic leukemia in children and adolescents: interim results of the Russian Ministry of Health approbation protocol

“…в качестве «мостика» перед трансплантацией костного мозга (ТКМ) для элиминации минимальной остаточной болезни (МОБ) [11,14]. Заметный успех был также достигнут при использовании иммунотерапии у детей с первичным ВП-ОЛЛ [15,16]. У первичных пациентов препарат используется в качестве дополнительного элемента лечения для детей с медленным ответом на терапию (МОБ-позитивная ремиссия в конце индукции) или с определенными неблагоприятными клиническими характеристиками (например, с перестройками KMT2A) с последующей ТКМ или без нее [15,16].…”

“…Заметный успех был также достигнут при использовании иммунотерапии у детей с первичным ВП-ОЛЛ [15,16]. У первичных пациентов препарат используется в качестве дополнительного элемента лечения для детей с медленным ответом на терапию (МОБ-позитивная ремиссия в конце индукции) или с определенными неблагоприятными клиническими характеристиками (например, с перестройками KMT2A) с последующей ТКМ или без нее [15,16]. Другим применением CD19-направленной терапии в первой линии является снижение интенсивности и токсичности лечения путем замены интенсивных курсов химиотерапии иммунотерапией, в частности у пациентов с пониженной толерант ностью к цитостатикам (например, у детей с синдромом Дауна) [15].…”

“…Основываясь на многообещающих результатах лечения рецидивов и рефрактерных форм BП-ОЛЛ [12,13], иммунотерапия блинатумомабом стала использоваться в протоколах для первичных больных BП-ОЛЛ [15,16,32,33]. Однако в большинстве исследований блинатумомаб использовался лишь для эскалации лечения или иногда в качестве замены интенсивной высокодозной химиотерапии у детей с плохим ответом, как с последующей ТКМ, так и без нее [15].…”

Blinatumomab as postremission therapy replaces consolidation and substantial parts of maintenance chemotherapy and results in stable MRD negativity in children with newly diagnosed B-lineage ALL

“… 1 Remarkable success was also achieved using immunotherapy in children with primary BCP-ALL. 4 5 Mostly, it is used as an additional treatment element for patients with a slow response to therapy 5 6 or with clinical high-risk characteristics (eg, infants with KMT2A gene rearrangements) with or without subsequent HSCT. 4 7 8 Another approach to targeting CD19 in first-line therapy is to reduce treatment intensity and toxicity by replacing intensive chemotherapy with immunotherapy, for example, in patients with reduced tolerance to the usual therapy (eg, in children with Down syndrome).…”

Further validation of poor prognosis for pediatric KMT2A-rearranged leukemia and the need for rapid integration of targeted therapies for these patients

“…Adults with KMT2A -r leukemia also have responded well to either blinatumomab or inotuzumab ( 16 ). Ongoing standard and high-risk B-ALL trials through COG will determine if blinatumomab and/or inotuzumab become the upfront pediatric standards of care, with upfront blinatumomab already gaining significant traction based on efficacy and tolerability in pediatric patients unfit to continue conventional chemotherapy and among adults treated on the E1910 study ( 17 , 18 ). Lineage switching of t(4;11) ALL to AML has been reported, but given the overwhelmingly positive data supporting upfront blinatumomab use, it must be assumed that subsequent KMT2A -r rearranged patients will receive upfront immunotherapy ( 19 ).…”