4 Quiet Revolutions at ASCO 2026 That Should Not Be Missed
In this article
ASCO 2026 preview · Volume 2 — in vivo CAR-T, cognitive survival, digital phase oncology, and value-based de-escalation
- The first revolution, produced within the patient's own body in multiple myeloma, is in vivo CAR-T cell therapy. KLN-1010 is the first cell therapy candidate that does not require lymphodepleting chemotherapy, with its first human data presented in the ASH plenary session in December 2025. The platform developed by Kelonia Therapeutics, acquired by Eli Lilly in April 2026, is a critical step toward democratizing cell therapy.
- The second revolution, shifting the definition of survival from an OS figure to "functional survival", is cognitive oncology. The ARACOG study (Abstract 5005) provides the first large body of randomized data comparing the cognitive side effect profiles of darolutamide and enzalutamide head to head in prostate cancer. ARSI selection for older patients will now be based not only on efficacy but also on cognitive side effects.
- The third revolution is digital phase oncology: SUPPORT+ (LBA12008), YES (Abstract 12009), digital health in childhood cancer survivors (Abstract 10003). Telehealth, mHealth, and digital biomarkers are now a main front at ASCO 2026, rather than a "subheading".
- The fourth revolution is value-based de-escalation: LBA6007 (a low-cost HNSCC alternative for resource-limited systems), OPTIMA (Abstract 500), REDUSE (Abstract 1004), and the CHALLENGE cost-effectiveness analysis (Abstract 3507). Clinical evidence for the philosophy of "less is more".
In vivo CAR-T: gene therapy produced in the body, ready to use off the shelf
Conventional ex vivo CAR-T therapy consists of multiple complex steps: collecting T cells from the patient (apheresis), modifying these cells in the laboratory with a viral vector, expanding them, administering lymphodepleting chemotherapy before returning them to the patient, and only then infusing them. This process takes weeks, can be carried out only at selected centers for logistical reasons, and places a substantial burden on the patient. This entire chain also explains why cell therapy remains so expensive, delayed, and inaccessible to the vast majority of the world.
The logic of in vivo CAR-T claims to eliminate this entire chain. In this method, specially engineered lentiviral particles delivered into the patient's body through an intravenous injection selectively enter circulating T cells; inside, they insert the CAR (chimeric antigen receptor) gene and tell the cells to transform themselves into CAR-T cells. In other words, the patient's own body becomes the CAR-T manufacturing laboratory. Because the cells do not leave the patient, apheresis is unnecessary. The first human data for this approach were announced in December 2025 for the experimental agent KLN-1010 in the plenary session of the ASH (American Society of Hematology) annual meeting.
The real meaning of these figures emerges when they are considered together, rather than alone. In conventional ex vivo CAR-T therapies, lymphodepleting chemotherapy given to the patient before infusion (usually fludarabine + cyclophosphamide) is critical for the expansion of modified T cells; it was thought that the cells would not persist if this step were omitted. The KLN-1010 data, however, even without lymphodepletion , showed that CAR-T cells reached peak expansion on day 15 and that T cells with a memory phenotype persisted in bone marrow and blood at the third month.
In April 2026, Eli Lilly announced that, by acquiring Kelonia Therapeutics, the developer of the in vivo CAR-T platform including KLN-1010, it had brought clinical development in this field under the roof of a major biopharmaceutical company. This is a concrete indication of in vivo CAR-T therapy's transition from academic interest to clinical development backed by capital at scale. While many major randomized trials of sequential treatment options for multiple myeloma will be presented during ASCO 2026 (MajesTEC-9 teclistamab and CARTITUDE-4 follow-up, covered in Volume 1), the underlying question the field will really discuss will be: if cell therapy can one day be reduced to an intravenous injection, how will we rethink the current treatment sequence?
The perspective of Turkey and international patients
Beyond clinical efficacy, the in vivo CAR-T concept raises the question of democratizing cell therapy. In Turkey, only a limited number of centers can still administer tisagenlecleucel and axicabtagene ciloleucel; for international patients (particularly the cohort from Central Asia, the Caucasus, and Middle Eastern countries), referral to Barcelona, Frankfurt, or Rotterdam is a clinical necessity. If the in vivo approach can compete with ex vivo products in terms of side effects and durability, CAR-T could become deliverable, from a logistical perspective, at any center where monoclonal antibodies are administered today — in an outpatient setting. This could resolve a cell therapy access problem spanning a decade.
"Brain-protective treatment": the cognitive axis of ARSI selection in prostate oncology
For many years, survival in oncology was summarized by a single figure — overall survival (OS) in years or months. This reductionist approach pushed aside the question of how survival was lived . The concept beginning to enter the oncology community's agenda as we approach the second half of the 2020s is functional survival: not only how long the patient lives, but how cognitively independent, socially functional, and professionally productive they remain during that time.
The most important ASCO 2026 data along this axis come from the Alliance ARACOG study (AFT-47, Abstract 5005): in older patients with castration-resistant prostate cancer, the first large randomized study directly comparing the cognitive side effect profiles of darolutamide and enzalutamide. For the clinical choice among three ARSIs (androgen receptor signaling inhibitors) — apalutamide, enzalutamide, darolutamide — for the first time, with cognitive function treated not as a secondary axis of survival but as the principal axis of survival , ARACOG frames its discussion around cognitive function.
Blood-brain barrier (BBB) crossing: High — through passive diffusion.
CNS distribution: Pronounced; measurable concentration in cerebrospinal fluid.
Cognitive side effect signal: Fatigue, reduced attention, and mild cognitive slowing have been reported in previous studies. More pronounced in older patients.
Blood-brain barrier (BBB) crossing: Very low — the molecule's structural design has been optimized to limit BBB permeability.
CNS distribution: Minimal; very low brain penetration in preclinical models.
Cognitive side effect signal: In Phase 3 ARAMIS and ARASENS data, the incidence of fatigue and neurological side effects is close to placebo.
BBB crossing: Intermediate — between enzalutamide and darolutamide.
CNS distribution: Limited, but the incidence of neurological side effects is being monitored clinically (rash and hypothyroidism are particularly prominent; the cognitive signal is milder).
ARACOG will make the definitive comparison of these three agents along the cognitive axis.
ARACOG's results will clarify one of the fundamental questions of everyday clinical practice in prostate oncology: if three ARSIs have the same or similar efficacy, which should be given to which patient? For a socially active prostate cancer patient over 75, with cognitive vulnerability related to advanced age (still working, driving, and managing their own financial decisions), darolutamide; for a younger patient without a concomitant cognitive disorder, the other two agents are also reasonable. Until now, this nuance rested on empirical knowledge; ARACOG will bring it onto a foundation of randomized clinical evidence.
Implications for OUR CLINICAL PRACTICE
In joint urology + medical oncology tumor boards, ARSI selection for older patients with castration-resistant prostate cancer will now require a three-stage assessment: (1) disease biology (HRR mutation status — discussed in the context of TALAPRO-3 in Volume 1), (2) age and cognitive reserve assessment, (3) patient preference and lifestyle. This framework should become part of the tumor board report structure after ARACOG data are published. It is also critical for international patient coordinators: choosing darolutamide in the cohort of male patients aged 70+ from the Middle East and Eastern Europe may provide a tangible advantage in terms of patient-reported quality of life endpoints.
The pediatric oncology connection — Abstract 10003
The concept of cognitive survival is not only for older patients. At ASCO 2026, Abstract 10003 will present data on a digital health intervention for comorbid insomnia and neurocognitive impairment in childhood cancer survivors . Pediatric oncology survivors who previously received chemotherapy, radiotherapy, and hematopoietic stem cell transplantation lag markedly behind the general population in cognitive dysfunction, sleep disorders, and psychosocial burden when they reach adulthood. This study tests the role of digital interventions in alleviating this burden — it should be read along the same intellectual axis as drozdogan.com's May 2026 article on sleep-proteomics-gastrointestinal cancer (Yangyang Liu, MSKCC, DDW 2026).
Digital phase oncology: telehealth, mHealth, and digital biomarkers are no longer a subheading
The 2020-2022 COVID-19 pandemic inevitably pushed oncology into telehealth and digital follow-up practice. It was thought these practices would retreat after the pandemic; instead, they became permanent. The ASCO 2026 program may be the most intensive year showing that digital health studies have become a front in their own right, rather than a "subheading". Three main stages:
Design: A digital self-management and clinical support intervention for patients with advanced cancer versus standard care — a randomized controlled trial.
Importance: The first large RCT measuring the value that managing the symptom burden of advanced cancer — pain, fatigue, anxiety, depression — with digital tools adds to standard care.
For Turkish practice: The scientific grounding of Memorial's protocols for long-distance follow-up of international patients.
Design: An mHealth intervention for AYA (adolescent and young adult, aged 18-39) breast cancer survivors.
Importance: The incidence of early-onset breast cancer is rising globally; in this cohort, quality of life, fertility concerns, professional reintegration, and psychosocial burden are layers that traditional oncology care fails to capture.
For Turkish practice: Clinical evidence for digital support tools aimed at young breast cancer patients.
Design: A digital health intervention for comorbid insomnia and neurocognitive impairment in childhood cancer survivors.
Importance: Establishing digital follow-up infrastructure as pediatric oncology survivors transition to adulthood.
For Turkish practice: Pediatric oncology survivorship clinics in Turkey are still being established; these data may serve as a reference for national program design.
The common feature of these three studies is this: none tests a new drug or chemotherapy regimen. All three, in the structure surrounding cancer treatment — symptom management, survival, psychosocial support — seek improvements through digital tools. This is a sign of maturity in the oncology community: seeing the patient's experience during and after treatment as a research question beyond drugs.
The practical meaning for international patient services in Turkey
A substantial proportion of patients arriving from abroad at Memorial Göztepe and other Turkish oncology centers — particularly the cohort from Central Asia, the Caucasus, and the Middle East — stay in Turkey for initial assessment and active treatment, then return to their countries. For these patients, long-term survivorship follow-up is inevitably conducted from a distance. Digital phase oncology studies (such as SUPPORT+) form a clinical evidence foundation precisely for this cohort: can a patient followed through an mHealth platform, periodic telehealth consultations, and ePRO questionnaires be managed safely and effectively without a physical clinic visit? ASCO 2026 data will provide a concrete answer to this question.
"Less is more": the cost, toxicity, and evidence foundation of the de-escalation philosophy
The main axis of oncology over the past 20 years has been built on "adding": add a new drug, intensify the dose, extend treatment duration, enrich the combination. This strategy increased efficacy, but created a sustainability problem in terms of toxicity, cost, and patient fatigue. In Volume 1, we touched on de-escalation studies such as SENOMAC and OPTIMA; in this article, under the umbrella of value-based oncology , we examine three new types of study.
Design: In patients with platinum-sensitive recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), ultra-low-dose immunotherapy + oral metronomic chemotherapy versus standard paclitaxel-carboplatin (Phase 3 randomized).
Importance: The potential to offer a low-cost alternative deliverable in an outpatient setting for healthcare systems with limited resources. Treatment cost is approximately 1/10 of the standard pembrolizumab + chemotherapy regimen.
For Turkish practice: Particularly meaningful within the SGK budget. Considering the ~5.000 annual head and neck cancer cases in Turkey, this concept will bring clear data to the reimbursement discussion.
Design: Spacing out denosumab doses in patients with bone metastases from solid tumors: q12w (every 12 weeks) versus standard q4w (every 4 weeks), Phase 3 non-inferiority in skeletal events.
Importance: If denosumab is reduced to one-sixth of the dose — 4-5 doses a year instead of 13 — patient clinic visits, nursing workload, and drug costs decrease dramatically.
For Turkish practice: An enormous budget impact from the SGK perspective. Denosumab is used in approximately 40.000 oncology patients annually in Turkey; if the q12w strategy proves non-inferior, this means annual savings of millions of TL nationwide.
Design: Test-guided chemotherapy in ER+/HER2- early-stage breast cancer with high clinical risk (Phase 3 non-inferiority). The European counterpart of TAILORx and RxPONDER.
Importance: Is it safe to omit chemotherapy in patients who appear clinically high risk but have low genomic risk on a multigene test such as Oncotype DX? OPTIMA provides the practical answer to this question.
For Turkish practice: It may influence reimbursement decisions for multigene tests in breast oncology; the cost-effectiveness of avoiding unnecessary chemotherapy exposure becomes clearer.
Design: For a structured exercise program after adjuvant chemotherapy for colon cancer, a cost-effectiveness analysis. The primary DFS outcome of the CHALLENGE study was announced as positive in 2025; this time, its economic evidence is being presented.
Importance: The first large RCT data proving a nonpharmacological intervention (a structured exercise program) in terms of both clinical benefit and cost-effectiveness.
For Turkish practice: Could exercise counseling for colon cancer survivors be included in health insurance coverage? The answer to this question is important for health policy.
The perspective of Turkish health economics
Turkey operates within a healthcare system in which the share of cancer care costs in the SGK budget rises every year. The value-based studies to be presented at ASCO 2026 — a low-cost HNSCC alternative, spacing out denosumab doses, test-guided chemotherapy omission, and the cost-effectiveness of lifestyle interventions — provide data with direct policy value for Turkey, as well as scientific interest. For healthcare systems tightening their belts, the philosophy of "less is more" is a necessity, rather than a clinical luxury. Memorial Göztepe and other Turkish oncology centers should systematically evaluate how these studies translate into local practice after ASCO 2026 — particularly proposals for alternative regimens in international patient treatment plans according to the coverage capacity of the insurance system in the patient's country.
DROZDOGAN Academy
Importance
The four axes covered in this second article of the ASCO 2026 preview series represent conceptual shifts that remain in the shadow of the drug-centered plenary news in our first article, yet have a long-term impact at least as great. In vivo CAR-T redefines how cell therapy is delivered; ARACOG reminds us that survival is function as well as duration; SUPPORT+ and other digital studies show oncology care expanding from the physical clinic into a digital ecosystem; and LBA6007, REDUSE, OPTIMA, and CHALLENGE together form the clinical evidence foundation for the philosophy of "less is more". These four axes tell us that oncology practice in the next decade will concern not only "which drug", but also "who, where, how, for how long, and at what cost".
Strengths
All four revolutions rest on different axes of methodological strength. The in vivo CAR-T data still come from a small sample of four patients, but offer biologically convincing depth — one hundred percent MRD negativity, cell expansion comparable to ex vivo therapies, and maintenance of a memory phenotype independent of lymphodepletion. The randomized Alliance ARACOG study is the first large head-to-head comparison testing differences in BBB crossing described in the pharmacology literature in the clinical phenotype. Digital studies such as SUPPORT+ and YES are randomized validations built on the substantial observational foundation of practice during COVID. LBA6007, REDUSE, and OPTIMA — all three are Phase 3, all three have non-inferiority or superiority designs, and all three provide datasets with a concrete budget impact in health economics.
Limitations
Each revolution carries its own methodological vulnerability. The in vivo CAR-T data are still very limited; it will take years to answer questions about long-term durability, the risk of secondary malignancy, and the course of resistant clones. ARACOG's cognitive outcome measures (MoCA, MMSE, patient-reported cognitive questionnaires) are debatable in terms of clinical significance — a statistical difference may not mean a real difference reflected in the patient's daily life. Digital phase oncology studies face a problem of unequal access — digital literacy, smartphone access, and internet infrastructure are limiting factors in cohorts with low socioeconomic status. The greatest risk for value-based de-escalation studies is that strategies found positive at ASCO cannot be applied to the right patient in the real world — for example, inappropriate use of the REDUSE q12w strategy in patients with high-risk bone metastases.
Impact on Clinical Practice
The translation into Turkish oncology practice will occur at four different speeds along four axes. In vivo CAR-T therapy is still in Phase 1; at least three to five years are needed for actual clinical use. ARACOG results will enter clinical guidelines within a few months of the congress presentation; darolutamide's position as the first choice in older patients with castration-resistant prostate cancer will strengthen. Digital phase oncology tools (mHealth, ePRO platforms) can be integrated into the international patient service infrastructure of tertiary centers such as Memorial Göztepe within this year — particularly for long-term remote follow-up of patients from Central Asia, the Caucasus, and the Middle East. Value-based de-escalation studies (REDUSE, OPTIMA, LBA6007) will bring direct data to SGK reimbursement discussions and serve as a reference for budget impact analyses by the Ministry of Health of the Republic of Turkey.
Future Questions
Questions that will open after the plenary presentations: for in vivo CAR-T — durability in larger samples, the incidence of CRS, expansion to targets beyond BCMA (CD19, GPRC5D), and whether solid tumor targets will be technically possible. For ARACOG — if cognitive outcomes are positioned as primary endpoints, will "cognitive side effects" become a new regulatory variable in drug approval processes? For digital oncology — how will mHealth interventions be included in insurance coverage, how will inequalities in health literacy be closed, and how will certification processes for AI-based symptom prediction tools take shape? For value-based oncology — could a structure such as a national "cancer treatment cost-effectiveness board" be established in Turkey; how could SGK decisions be brought into an evidence-based, value-based oncology framework? These questions will largely define the oncology research agenda for the next five years.
Scientific Sources
- American Society of Clinical Oncology. ASCO Annual Meeting 2026 Scientific Program. 29 May - 2 June 2026, McCormick Place, Chicago. asco.org/meetings
- Kelonia Therapeutics. Kelonia Therapeutics Presents First-in-Human Data from Phase 1 inMMyCAR Study of KLN-1010 in vivo BCMA CAR-T Therapy at the American Society of Hematology (ASH) 2025 Annual Meeting. Press release, 9 December 2025.
- Eli Lilly and Company. Lilly to acquire Kelonia Therapeutics to advance in vivo CAR-T cell therapies. PR Newswire press release, 20 April 2026.
- Harrison S, Ho PJ, Lim S-L, et al. MRD-negative outcomes following a novel, in vivo gene therapy generating anti-BCMA CAR T-cells in patients with RRMM: preliminary results from inMMyCAR, the first-in-human phase 1 study of KLN-1010. Blood 2025;146(suppl 1):LBA-1.
- Alliance for Clinical Trials in Oncology. AFT-47 — A Randomized, Double-Blind Phase III Study of Darolutamide vs Enzalutamide in Patients with Castration-Resistant Prostate Cancer: Cognitive Function Evaluation (ARACOG). ASCO 2026 Abstract 5005.
- Bartsch R, Berger A, Bergmann M, et al. Comparative blood-brain barrier penetration and cognitive safety profile of androgen receptor signaling inhibitors. European Urology Focus 2024;10(3):295-307.
- Fizazi K, Shore N, Tammela TL, et al. Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer (ARAMIS). New England Journal of Medicine 2019;380:1235-1246.
- Smith MR, Hussain M, Saad F, et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer (ARASENS). New England Journal of Medicine 2022;386:1132-1142.
- ASCO Annual Meeting 2026 Late-Breaking Abstract LBA12008 — SUPPORT+: A digital self-management and clinician support intervention for advanced cancer (RCT).
- ASCO Annual Meeting 2026 Abstract 12009 — YES: A digital mHealth intervention for adolescent and young adult (AYA) breast cancer survivors.
- ASCO Annual Meeting 2026 Abstract 10003 — A digital health intervention for comorbid insomnia and neurocognitive impairment in childhood cancer survivors.
- ASCO Annual Meeting 2026 Late-Breaking Abstract LBA6007 — Ultra-low dose immunotherapy plus oral metronomic chemotherapy versus paclitaxel-carboplatin in platinum-sensitive recurrent/metastatic HNSCC (phase 3).
- ASCO Annual Meeting 2026 Abstract 1004 — SAKK 96/12 REDUSE: Denosumab q12w vs q4w in solid tumor bone metastases (phase 3 non-inferiority).
- ASCO Annual Meeting 2026 Abstract 500 — OPTIMA: Test-directed chemotherapy in high clinical-risk ER+/HER2- early breast cancer (phase 3 non-inferiority).
- ASCO Annual Meeting 2026 Abstract 3507 — CHALLENGE trial cost-effectiveness analysis: structured exercise after adjuvant chemotherapy in colon cancer.
- Courneya KS, Vardy JL, O'Callaghan CJ, et al. Structured Exercise after Adjuvant Chemotherapy for Colon Cancer (CHALLENGE). New England Journal of Medicine 2025;393(13):1289-1299. (CHALLENGE primary DFS analysis.)
- Stopeck AT, Lipton A, Body JJ, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer. Journal of Clinical Oncology 2010;28(35):5132-5139. (Foundational efficacy literature for denosumab q4w.)
- drozdogan.com oncology editorial team. ASCO 2026 Preview · Volume 1 — Plenary 5, 7 thematic categories, impact map for Turkish clinical practice. May 2026.
Was this article helpful?
Your feedback helps us improve our content.
Reader comments
Share your comment
Your name and comment are published only after administrator approval. Your email address is never shown to visitors.
Be the first to comment.