Malaysian Society of Haematology

12/02/2026

Paroxysmal Nocturnal Haemoglobinuria (PNH): Evolving Complement Inhibition Strategies

Paroxysmal nocturnal haemoglobinuria remains a rare but high-impact complement-mediated disorder characterised by chronic intravascular haemolysis and a disproportionate risk of thrombosis in atypical sites. While anti-C5 therapy has transformed survival over the past 15 years, a significant proportion of patients continue to experience persistent anaemia due to residual extravascular haemolysis.

The biological rationale for therapeutic evolution is clear. C5 inhibition (eculizumab, ravulizumab) prevents membrane attack complex formation and controls intravascular haemolysis, but does not fully suppress upstream C3 activation. This has driven development of proximal complement inhibitors targeting C3 or the alternative pathway (factor B, factor D), with the aim of improving haemoglobin normalisation and transfusion independence.

Recent phase 3 data have expanded the evidence base:

• Eculizumab (TRIUMPH, SHEPHERD; phase 3) demonstrated marked LDH reduction, reduced transfusion need, and significant reduction in thrombotic events.
• Ravulizumab (Studies 301/302; phase 3) showed non-inferiority to eculizumab with extended 8-week dosing intervals.
• Pegcetacoplan (PEGASUS; phase 3) improved haemoglobin by approximately 3–4 g/dL in patients with persistent anaemia on C5 inhibition and increased transfusion avoidance.
• Iptacopan (APPLY-PNH; phase 3) demonstrated at least 2 g/dL haemoglobin increase in the majority of patients switched from C5 inhibitors, with high rates of transfusion independence.
• Danicopan (ALPHA; phase 3) improved haemoglobin when added to C5 blockade in patients with extravascular haemolysis.

International guidance, including ASH and European consensus statements, continues to recognise complement inhibition as the foundation of disease-modifying therapy, with treatment selection increasingly individualised according to haemolytic control, anaemia burden, thrombosis risk, route of administration, and patient preference.

For Malaysian practice, key considerations include vaccination protocols against Neisseria species, monitoring for breakthrough haemolysis, and the practical realities of treatment access. As proximal inhibition becomes more widely available, clinicians will need to consider whether persistent anaemia on C5 blockade warrants add-on therapy or switching strategy.

PNH has transitioned from a life-limiting haemolytic disorder to a chronic, biologically targetable condition. The current challenge is no longer whether to inhibit complement, but how best to sequence and individualise therapy for durable disease control with minimal treatment burden.

08/02/2026

Relapsed and refractory DLBCL remains one of the most challenging areas in contemporary haematology, particularly in patients with early relapse after R-CHOP, high-risk extranodal disease, or rapidly progressive chemotherapy-refractory lymphoma where autologous transplant or CAR-T are not feasible.

Recent trial and real-world data have highlighted Glofitamab, a CD20×CD3 bispecific antibody, as a clinically meaningful option in this setting. Biologically, glofitamab enables potent T-cell–mediated cytotoxicity against CD20-expressing lymphoma cells, with activity that appears less dependent on conventional chemosensitivity. In the randomised phase III STARGLO study, glofitamab + GEMOX demonstrated superior disease control compared with rituximab-GEMOX in transplant-ineligible relapsed/refractory DLBCL, with higher complete remission rates and a significant reduction in the risk of death.

These data were reinforced by regional real-world experience presented during the event, including 4 relapsed/refractory DLBCL cases from Subang Jaya Medical Centre presented by Prof Ng Soo Chin, and 11 cases from Sunway Medical Centre presented by Ng Ho Kim Wah. Collectively, these cases encompassed early post–R-CHOP relapse, bulky extranodal disease (including cardiac and testicular involvement), and heavily pre-treated, chemotherapy-refractory lymphoma. Several patients achieved rapid complete metabolic remission within 2–3 cycles of glofitamab-based therapy, illustrating its clinical activity outside trial settings and its role when CAR-T was limited by disease tempo, access, or cost.

From a practical standpoint, several consistent themes emerged:

Cytokine release syndrome is typically early and manageable with step-up dosing and appropriate monitoring

Infection risk and hypogammaglobulinaemia become key considerations with ongoing therapy

Fixed-duration treatment (often ~12 months) is commonly adopted to balance disease control against cumulative immune toxicity

As reflected in evolving international guidance, including perspectives from the American Society of Hematology, CD20×CD3 bispecific antibodies are now firmly embedded in the relapsed/refractory DLBCL treatment paradigm. The integration of phase III trial evidence with Malaysian real-world case series underscores glofitamab’s role as a pragmatic, off-the-shelf immunotherapy for patients with otherwise limited therapeutic pathways.

07/02/2026

Relapsed and refractory diffuse large B-cell lymphoma (RR DLBCL) remains a major unmet need in routine practice. Patients with primary refractory disease or early relapse after R-CHOP often derive limited benefit from conventional salvage chemotherapy, and access to CAR-T therapy may be constrained by eligibility, toxicity, cost, or manufacturing timelines. This has driven interest in off-the-shelf immunotherapies capable of inducing deep remissions without prolonged delay.

Glofitamab is a CD20×CD3 bispecific antibody designed to redirect endogenous T cells against malignant B cells. The biological rationale mirrors CAR-T therapy—early, profound cytoreduction through T-cell–mediated cytotoxicity—while avoiding the logistical barriers of autologous cell manufacture. Clinically, this approach has consistently shown that depth of response, particularly complete remission (CR), is the key determinant of durable benefit.

The phase III STARGLO trial provides the strongest evidence to date for this strategy. In a high-risk RR DLBCL population (with a large proportion of primary refractory disease), glofitamab plus GemOx was compared with rituximab-GemOx and demonstrated:

A significant overall survival benefit (median OS approximately doubled)

Markedly higher CR rates (approaching ~60%), comparable to those seen with CAR-T in similar settings

A clear plateau in survival curves, suggesting durable long-term disease control in a meaningful subset
Toxicities were predictable and manageable, with cytopenias (largely chemotherapy-related) and cytokine release syndrome mainly confined to early cycles and mitigated by step-up dosing.

From a real-world perspective, these data support bispecific antibodies—particularly glofitamab-based regimens—as a credible second-line option for RR DLBCL, especially where CAR-T access is delayed or not feasible. Current international guidelines (e.g. ASH, ESMO) increasingly recognise bispecific antibodies as an important component of the evolving treatment algorithm. For clinicians, the key message is clear: using highly effective immune therapies earlier, with the aim of achieving CR, may meaningfully expand the curative fraction in RR DLBCL.

03/02/2026

Ponatinib in the front-line treatment of Philadelphia chromosome–positive ALL: an evolving standard

Philadelphia chromosome–positive acute lymphoblastic leukaemia (Ph+ ALL) remains a biologically high-risk subtype, despite major gains with BCR-ABL1 tyrosine kinase inhibitors (TKIs). A key unmet need has been achieving *early, deep molecular remissions* to reduce relapse risk and refine transplant decision-making. Recent regulatory developments in Europe highlight a shift towards addressing this gap earlier in the disease course.

The EMA Committee for Medicinal Products for Human Use (CHMP) has recommended expanding the indication of ponatinib—a third-generation BCR-ABL1 TKI with activity against all known kinase-domain mutations, including T315I—into the newly diagnosed adult Ph+ ALL setting, in combination with low-intensity chemotherapy . This recommendation is informed by randomised phase III data rather than post-resistance extrapolation alone.

Key clinical evidence comes from the phase III PhALLCON trial, which randomised adults with newly diagnosed Ph+ ALL to ponatinib versus imatinib, each with reduced-intensity chemotherapy:

* MRD-negative complete remission at end of induction: 34% with ponatinib vs 17% with imatinib
* Overall MRD negativity (regardless of CR): 43% vs 21%
* Event-free survival: immature, but trending in favour of ponatinib
* Benefits were consistent across p190 and p210 BCR-ABL1 isoforms
* Vascular toxicity remains the key safety signal, reinforcing the need for cardiovascular risk assessment and monitoring

From a practice perspective, these data support the concept that *front-loading the most potent TKI* can meaningfully deepen early molecular responses, with potential implications for:

* Risk-adapted use of allogeneic stem cell transplantation
* Treatment de-intensification strategies in selected patients
* Managing patients with high-risk biology or poor early molecular clearance

While longer follow-up is needed for overall survival and relapse outcomes, the emerging evidence positions ponatinib as a credible front-line option in Ph+ ALL when used judiciously, balancing molecular efficacy against cardiovascular risk—consistent with contemporary ASH and European practice trends.

31/01/2026

In just 2 months to go, register now, enquire at the link - https://www.hematology.org/meetings/highlights-of-ash-in-asia-pacific

31/01/2026

Systemic lupus erythematosus (SLE) remains a clinically heterogeneous disease, and haematological manifestations such as leukopenia, lymphopenia, thrombocytopenia and autoimmune haemolytic anaemia continue to pose real challenges in day-to-day practice. These abnormalities are not merely laboratory curiosities; they are markers of immune dysregulation, contribute to morbidity, and often drive prolonged corticosteroid exposure with its attendant risks.

Recent data discussed in a national lecture highlight the evolving role of anifrolumab, a monoclonal antibody targeting the type I interferon receptor, in addressing this unmet need. Given the central role of interferon signalling in SLE pathogenesis, blockade of this pathway offers a biologically coherent approach, particularly for multi-system and haematologically active disease.

Key clinical evidence includes post-hoc pooled analyses from the TULIP-1 and TULIP-2 Phase III trials, together with their long-term extension (up to four years), demonstrating sustained improvement across haematological domains. Patients treated with anifrolumab showed higher rates of normalisation of lymphocyte counts, improvements in leukopenia, platelet counts and haemoglobin levels, with effects seen early and maintained long term. Importantly, these benefits were accompanied by meaningful steroid-sparing, a priority outcome for many clinicians. These findings are complemented by emerging Malaysian real-world case series, reinforcing their relevance in local practice.

From a guideline perspective, the 2024 ACR recommendations continue to frame management of SLE-related cytopenias around disease severity and bleeding risk, with established roles for corticosteroids, conventional immunosuppressants, IVIG and CD20-directed therapy. Within this landscape, anifrolumab represents an additional, evidence-based option for selected patients with active SLE and haematological involvement, particularly where disease control and steroid reduction are key objectives. For clinicians managing complex SLE, these data support a more targeted, mechanism-driven approach aligned with contemporary international guidance and real-world priorities.

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10/11/2025

Warm greetings from the Malaysian Society of Haematology (MSH)!

We are delighted to announce that MSH will host the Highlights of ASH in Asia-Pacific 2026, in collaboration with the American Society of Hematology (ASH).

The event will take place at the Shangri-La Kuala Lumpur on April 10–11, 2026.

As ASH describes it:
“Highlights of ASH in Asia-Pacific brings global hematology leaders together for two days in Kuala Lumpur, Malaysia. Discuss the most influential and novel research from the latest ASH Annual Meeting, spanning a wide range of topics. Connect with top experts in person and learn how to apply the latest research to your own work.”

Registration is now open via the ASH website:
https://www.hematology.org/meetings/highlights-of-ash-in-asia-pacific

We look forward to welcoming haematology colleagues and researchers from around the region to Kuala Lumpur for two days of learning, collaboration, and discovery.

24/04/2025

Opening ceremony

24/04/2025

Opening ceremony by Prof Gan Gin Gin, President of the MSH, and Dr Lim Su Hong, organising Chairman

24/04/2025

Panel discussion on AML , chaired by Dr Ng Soo Chin

24/04/2025

Dr Guan's presentation on elderly AML

24/04/2025

Dato Chang's talk on High risk AML