In this episode, Prof. Robin Foà, Prof. Filippo Milano and Prof. Sabina Chiaretti explore the first results of a worldwide randomized phase 3 trial that challenges a long-standing paradigm in adult Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL): the necessity of frontline chemotherapy. The discussion focuses on a direct comparison between a fully chemo-free strategy—combining Ponatinib and Blinatumomab—and the conventional standard of care based on Imatinib plus chemotherapy.

The trial enrolled 236 patients with no upper age limit and introduced age-adapted dosing of Ponatinib alongside strictly biology-driven criteria for allogeneic transplantation, based on molecular response, ABL1 mutations, and the Ikaros-plus genotype. Intensified central nervous system prophylaxis addressed the historically high risk of CNS relapse in this disease.

The speakers highlight the superiority of the chemo-free arm, which achieved higher hematological and molecular remission rates, improved event-free survival, and a marked reduction in the need for transplantation. These benefits were accompanied by better tolerability, with fewer severe adverse events and no excess cardiovascular toxicity compared with chemotherapy.

Looking ahead, the episode reflects on the broader clinical implications of these findings, particularly for elderly patients and those unfit for intensive therapy. The discussion also opens the door to the possibility of long-term treatment-free remission in patients achieving deep and durable molecular responses, while acknowledging ongoing challenges in global access to advanced diagnostics and targeted therapies.

A concise yet in-depth conversation on how precision medicine is reshaping the future of Ph+ ALL—moving the field closer to effective, chemotherapy-free frontline care.

In this episode, Prof. Robin Foà and Dr. Filippo Milano sit down with Dr. Mazyar Shadman, a leading voice in immunotherapy and one of the foremost experts in chronic lymphocytic leukemia (CLL). Together, they explore how rapidly—and profoundly—the therapeutic landscape of CLL has transformed, moving away from chemo-immunotherapy toward a new era defined entirely by targeted agents.

The conversation opens with a reflection on the radical shift that has occurred in frontline management. Where fludarabine-based regimens once dominated the care of younger and fit patients, the field has now embraced treatments that no longer rely on chemotherapy at all. Randomized studies consistently show improved progression-free survival—and in some cases overall survival—making targeted therapies the undisputed standard in countries where access is guaranteed.

Against this backdrop, the speakers examine the evolving first-line strategies: continuous BTK inhibition; fixed-duration venetoclax plus obinutuzumab; and the fully oral combination of ibrutinib and venetoclax. The recent CLL17 trial, a plenary abstract at ASH, provides one of the first head-to-head comparisons among these approaches. Early results suggest that fixed-duration treatments are not inferior to continuous BTK inhibition, underscoring how meaningful “time off therapy” has become for both patients and clinicians.

A central theme of the episode is the complexity behind treatment selection. Age, comorbidities, logistical constraints, and patient preference all interplay—yet Dr. Shadman emphasizes that even in older individuals, therapeutic choices should not be dictated by age alone. For some, the simplicity of a continuous oral regimen is preferable; for others, the goal of achieving deep remission and eventually stopping therapy is paramount. Prognostic markers, particularly TP53 disruption, continue to inform expectations and guide nuanced discussions around the trade-offs between durability and freedom from treatment.

The dialogue then turns to measurable residual disease (MRD). Although MRD negativity remains an important biological milestone, Dr. Shadman cautions against extending therapy beyond predefined durations solely to chase deeper responses—except in selected high-risk settings. Ongoing studies like CLL18 may soon clarify whether MRD-guided strategies can outperform fixed-duration regimens.

One of the most challenging areas discussed is the management of double-refractory CLL. CAR-T cell therapy, while transformative in other lymphoid malignancies, has delivered only modest long-term outcomes in CLL. Early referral is critical, ideally while patients are beginning treatment with the non-covalent BTK inhibitor pirtobrutinib. Real-world data suggest that cytoreduction and disease control before CAR-T may be key to improving responses. Allogeneic transplant, though reserved for the most refractory cases, remains a necessary option for younger patients when CAR-T is not accessible or feasible.

In closing, the speakers reflect on the ultimate goal of therapy—whether cure or functional cure—and how this must be tailored to the individual sitting in front of the clinician. For some, decades of remission represent success; for others, especially the very elderly, sustained disease control may be an equally meaningful outcome. Yet global inequities remain stark: while some countries benefit from cutting-edge targeted agents, many regions still rely on chemotherapy due to economic constraints.

This episode offers a thoughtful, forward-looking examination of where CLL therapy stands today—an arena shaped by scientific progress, clinical judgment, and the persistent drive to offer patients treatments that are not only effective but also aligned with their lives and priorities.

In this episode, Prof. Robin Foà and Dr. Filippo Milano are joined by Dr. Fred Appelbaum from the Fred Hutchinson Cancer Center to reflect on the persistent challenges and evolving landscape of acute myeloid leukemia (AML). Unlike other hematologic malignancies that have seen major therapeutic revolutions, AML remains bound to the traditional 7+3 regimen, a reminder of how complex its biology truly is.

The conversation delves into the biological roots of AML, emphasizing that the disease originates in the myeloid stem cell—an essential element of hematopoiesis that cannot be eradicated without profound consequences. This fundamental limitation has slowed progress compared with CML, CLL, or ALL, where targeted therapies have reshaped outcomes. Dr. Appelbaum reflects on the need to understand the molecular journey from normal stem cells to leukemic clones, envisioning future treatments capable of selectively eliminating malignant mutations while preserving healthy hematopoiesis.

A major theme of the discussion is the impact of Venetoclax, which has transformed induction therapy for elderly patients, offering higher remission rates and better tolerability. Yet, the question remains whether this improvement translates into cure or simply extends survival. Dr. Milano highlights its role as a bridge to transplant, while both he and Prof. Foà note the growing challenge of Venetoclax resistance and the need for more durable solutions.

The debate then turns to the role of transplantation in intermediate-risk AML. When should patients undergo transplant in first remission (CR1), and how should minimal residual disease (MRD) guide this decision? While studies suggest comparable outcomes between early and delayed transplantation, the practical reality is more nuanced, depending on MRD status, patient age, and access to specialized centers. Prof. Foà voices caution about relying on non-standardized, in-house MRD assays, stressing the ethical and clinical importance of centralized and validated methodologies.

Throughout the discussion, the speakers underscore how scientific progress in AML remains uneven—marked by breakthroughs like Venetoclax but constrained by the disease’s intrinsic biology. As the episode closes, they draw inspiration from the success story of acute promyelocytic leukemia (APL), once one of the deadliest forms of AML and now often cured without chemotherapy or transplant.

This dialogue is a candid examination of both frustration and hope—a reminder that even in areas where progress has lagged, persistent research and collaboration continue to push the boundaries of what is possible in the treatment of AML.

In this episode, Prof. Robin Foà and Dr. Filippo Milano look back on twenty-five years of remarkable progress in the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Once regarded as one of the most devastating hematologic malignancies, with prognosis considered among the worst in oncology, Ph+ ALL has undergone a dramatic transformation thanks to targeted therapies and innovative treatment strategies.

The conversation traces the pioneering decision to replace intensive chemotherapy with tyrosine kinase inhibitors and steroids, a bold approach that opened the way to higher remission rates and better tolerability, especially for older patients. From the early use of Imatinib to the evolution toward second- and third-generation TKIs, this paradigm shift has steadily improved outcomes and reshaped clinical practice. The discussion also highlights the D-ALBA study, where Dasatinib combined with Blinatumomab marked a new era by eliminating both induction and consolidation chemotherapy while achieving durable survival in the majority of patients.

Foà and Milano explore how minimal residual disease monitoring has become central to guiding therapy and reconsidering the role of transplant, once seen as the only curative option. They also reflect on the challenges that remain, including unequal access to modern therapies and the need for standardized laboratory infrastructures worldwide. While CAR-T cells play an expanding role in other leukemias, their use in Ph+ ALL remains limited in the frontline setting, reinforcing the centrality of TKIs and immunotherapy as the foundation of treatment.

This dialogue is both a scientific journey and a story of hope, showing how determined research, clinical innovation, and international collaboration have turned a disease once defined by despair into one where cure is now a realistic possibility for many patients.

In this episode, we delve into the evolving landscape of Acute Lymphoblastic Leukemia (ALL) treatment, with a focus on cutting-edge therapies and their impact on patient outcomes. We explore the rapid integration of CAR T-cell therapy, now being used earlier in treatment and its effects on survival rates. The discussion also addresses the shifting role of allogeneic transplantation, particularly in light of the economic and clinical advantages of newer therapies. We highlight the importance of minimal residual disease (MRD) monitoring and its ability to guide treatment decisions, potentially sparing patients from invasive procedures. Additionally, we examine the transformative effects of immunotherapies like blinatumomab and inotuzumab, and their role in reducing the reliance on traditional chemotherapy and transplantation. As the field continues to evolve, we consider the future of ALL treatment, including the challenges posed by economic constraints and the move toward personalized medicine.

Tune in for an in-depth analysis of these groundbreaking advances in ALL therapy and their potential to redefine treatment paradigms.

In this episode, we delve into the transformative changes in allogeneic stem cell transplantation (SCT), a treatment once seen as a last resort for patients but now experiencing a renaissance. Despite the rise of therapies like immunotherapy and CAR-T cells, SCT continues to evolve and remains crucial, particularly with recent breakthroughs. A key focus of the discussion is the introduction of post-transplant cyclophosphamide (PTCy), a groundbreaking advancement in SCT that significantly reduces the incidence of graft-versus-host disease (GVHD), a major complication. PTCy has shown extremely low rates of both acute and chronic GVHD in randomized clinical trials, a major shift from traditional immunosuppressive therapies. While concerns were raised about the potential for increased relapse due to the elimination of reactive T-cells, studies have shown no evidence of an increased relapse risk, making PTCy a game changer.

The use of PTCy has also expanded the donor pool, enabling the use of alternative donors such as mismatched relatives and haploidentical donors, which was unthinkable just five years ago. This expansion addresses the global challenge of finding compatible donors, especially for patients from underrepresented ethnic backgrounds or regions with poorly organized donor registries. Additionally, SCT is now being reconsidered as a first-line treatment for several hematologic conditions, thanks to reduced toxicity and the possibility of minimizing pre-transplant chemotherapy. This has also made SCT an option for patients over 75, although careful cardiological evaluation is essential due to potential heart risks associated with cyclophosphamide.

Despite the rise of novel therapies, SCT remains a cornerstone in the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), particularly for older patients. With advancements in post-transplant care and a better understanding of the microbiome’s influence, SCT will continue to play a pivotal role in treating these diseases. Listen to learn more about how SCT is evolving, maintaining its relevance, and offering hope to patients worldwide.

In this episode of Hematology Pills, Dr. Marco Ruella, Prof. Robin Foà, and Dr. Filippo Milano dive into the challenges of CAR T-cell therapy resistance. They explore key resistance mechanisms, including T-cell dysfunction, the tumor microenvironment, and antigen loss, such as CD19 in relapsed ALL. Dr. Ruella discusses promising strategies to overcome these hurdles, like dual-targeting approaches, and highlights the importance of improving CAR T-cell product quality and monitoring in clinical settings. The episode also touches on the inflammatory side effects, like cytokine release syndrome (CRS) and neurotoxicity (ICANS), and their potential for enhancing the anti-tumor effect. Tune in for a deep dive into the future of CAR T-cell therapies and their evolving role in cancer treatment.

In this episode of Hematology Pills, Professor Robin Foà speaks with Dr. Filippo Milano and Dr. Rahul Banerjee about the current role of CAR-T cell therapy in the treatment of multiple myeloma. The discussion touches on key aspects such as therapeutic potential, toxicity management, and the practical issues related to access. Aimed at clinicians and healthcare professionals, the episode provides a clear overview of both opportunities and limitations of this evolving approach.

Join Prof. Robin Foà (Sapienza University of Rome) and Dr.Filippo Milano (Fred Hutchinson Cancer Center, Seattle) as they explore the evolving landscape of CAR-T cell therapies. This episode of Hematology Pills offers concise yet profound insights into the challenges and opportunities surrounding CAR-T treatments, from access and sustainability to innovation and clinical advancements.With a focus on real-world applications, the discussion highlights key issues such as treatment accessibility, cost-effectiveness, long-term outcomes, and the future of CAR-T in autoimmune diseases.

In the inaugural episode of our hematology podcast, Professor Robin Foà(Emeritus Professor of Hematology, Sapienza University of Rome) and Dr. Filippo Milano (Associate Professor, Fred Hutchinson Cancer Center, Seattle) explore the groundbreaking advances in gene therapy and the pressing ethical dilemmas surrounding patient access. From the high costs and insurance hurdles in the U.S. to the impact on underserved populations, this discussion sheds light into the complex landscape of innovative treatments and equitable care. Join us for a thought-provoking conversation that bridges scientific innovation and real-world challenges in hematology.