Relapsed and Refractory Blood Cancers: Treatment

Relapsed blood cancer treatment

A relapse is a situation where the cancer disease reoccurs after a period of time perhaps when it has slightly improved or gone into remission. In progressing to view relating to blood cancer for example leukemia, lymphoma or multiple myeloma relapse may occur because:

• There was still evidence of cancer cells post-treatment.
• There was always the evolution of the disease so as to develop immunity to previous treatments.

Refractory leukemia treatment

Refractory leukemia is leukemia that resists usual therapy or relapses soon after a remission is achieved. Treatment is based on the leukemia type (AML, ALL, CML, CLL), patient age, health, genetic mutation, and prior therapies. This article provides an exhaustive list of present and pending treatments for refractory leukemia:

Re-induction Chemotherapy

• Applied in: AML and ALL.
• Objective: Obtain a second remission with alternative or escalated chemotherapy drugs.

Targeted Therapy

For leukemias with certain mutations or markers:

• FLT3
• IDH1/2
• BCR-ABL
• BTK

Immunotherapy

CAR-T Cell Therapy:

• Utilized in: Refractory B-cell ALL, certain cases of CLL and NHL.
• Examples: Tisagenlecleucel (Kymriah), Brexucabtagene autoleucel (Tecartus).

Bispecific T-cell Engagers (BiTEs):

• Example: Blinatumomab (CD19/CD3) for B-cell ALL.

Monoclonal Antibodies:

Examples:

• Inotuzumab ozogamicin (anti-CD22) for B-ALL.
• Rituximab for CD20+ CLL.

Hypomethylating Agents (HMAs)

• Utilized in elderly/unfit AML and MDS patients.
• Drugs: Azacitidine, Decitabine — often in combination with Venetoclax (BCL2 inhibitor).

BCL2 Inhibition

Venetoclax:

• Active in AML, particularly when used with HMAs or low-dose cytarabine.
• Also applied in CLL.

Allogeneic Stem Cell Transplant (HSCT)

• Potentially curative in most forms of refractory leukemia.
• Ideal for young, healthy patients with a matched donor.
• Involves high-dose chemo/radiation and then infusion of stem cells from a donor.

What is relapsed cancer?

Relapsed cancer is cancer that recurs after remission — that is, the disease had initially responded to therapy and was dormant or not detectable for some period of time before eventually returning either at the original site or somewhere else in the body.

Important Points Regarding Relapsed Cancer

Remission initially, followed by relapse:

A patient usually enters a state of partial or complete remission following initial treatment. Relapse is when cancer cells that were still in the body (usually invisible) start growing again.

Relapse vs. Refractory:

• Relapsed = Cancer comes back after responding to treatment.
• Refractory = Cancer never responded or got worse on treatment.
• Timing:
• Early relapse: Within 6–12 months of treatment. Usually more aggressive.
• Late relapse: More than a year after. Can be more treatable.

Treatment for relapsed lymphoma

Treatment for lymphoma relapse varies with the type of lymphoma, the patient's age and condition, the time to relapse after first treatment, and the previous treatment.

Relapsed Hodgkin Lymphoma (HL)

First-Line Relapse Treatment

• High-dose chemotherapy + Autologous Stem Cell Transplant (ASCT)
• Reference treatment for relapsed/refractory HL.
• Routine regimens prior to transplant: ICE, DHAP, ESHAP, GDP.
• If remission is obtained → go to ASCT (patient's stem cells).

Post-Transplant Choices (for relapse following ASCT)

• Brentuximab vedotin (anti-CD30 antibody-drug conjugate)

Immunologic checkpoint inhibitors:

• Nivolumab or Pembrolizumab (particularly in relapsed/refractory HL)
• Allogeneic stem cell transplant (from donor) for certain patients

Clinical Trials

• CAR-T cell therapy (e.g., targeting CD30)
• New immunotherapies and targeted therapies

Relapsed Non-Hodgkin Lymphoma (NHL)

Subtypes significantly:

A. Aggressive NHL (e.g., Diffuse Large B-cell Lymphoma – DLBCL)

• Salvage chemotherapy + ASCT
• Regimens: R-ICE, R-DHAP, R-GDP
• If chemo-sensitive, go to ASCT
• CAR-T cell therapy

FDA-approved for DLBCL after 2+ lines of therapy:

• Axicabtagene ciloleucel (Yescarta)
• Lisocabtagene maraleucel (Breyanzi)
• Polatuzumab vedotin + bendamustine + rituximab (for transplant-ineligible)

B. Indolent NHL (e.g., Follicular Lymphoma)

• Re-treatment with prior regimen if long remission (>2 years)

New targeted agents:

• PI3K inhibitors (e.g., Copanlisib, Duvelisib)
• EZH2 inhibitors (e.g., Tazemetostat)
• Lenalidomide + rituximab (R^2 regimen)
• Radioimmunotherapy (e.g., 90Y-ibritumomab tiuxetan)

CAR-T Cell Therapy

• Game-changer for aggressive and relapsed/refractory lymphomas.
• Personalized: Patient's own T cells are engineered to target cancer cells.

Indications:

• DLBCL refractory to ≥2 lines of therapy
• Certain transformed or high-grade lymphomas

FDA-approved CAR-T products:

• Yescarta, Kymriah, Breyanzi

Allogeneic Stem Cell Transplant

Reserved if:

• Relapse following autologous transplant
• High-risk or chemo-refractory disease
• Available donor
• Lies potential cure but risks are greater (GVHD, infections)

Palliative and Supportive Care

In frail or elderly patients who are neither transplant nor CAR-T candidates:

• Symptom control
• Palliative chemotherapy or radiation
• Emotional and psychosocial support

Relapsed vs refractory cancer

Relapsed Cancer

• Relapsed cancer is a condition where the cancer has recurred following partial or complete improvement or remission. 
• The patient had responded initially to treatment—either partially or entirely—and the cancer went undetectable or dormant. 
• However, after a while, cancer cells that were not completely killed start to proliferate again, causing the cancer to recur. 
• Relapse may occur weeks, months, or years following treatment termination. 
• Depending upon the duration of remission and on the cause of relapse, the same or a different treatment is employed.

Refractory Cancer

• Refractory cancer, in contrast, refers to cancer that is unresponsive to treatment from the onset or advances during therapy. 
• Here, the cancer is said to be resistant to the therapy employed. 
• There can be minimal or no decrease in size of the tumor, or it might progress in spite of undergoing standard treatments. 
• Refractory cancer is often harder to manage since it does not react to standard treatments, and novel approaches like new drug combinations, immunotherapy, CAR-T cell therapy, or clinical trials are necessary.

New treatments for blood cancer

New therapies for blood cancer have evolved at a fast pace over the last few years, especially in fields such as targeted therapy, immunotherapy, and cell-based therapy. These treatments are enhancing patient outcomes with leukemia, lymphoma, and multiple myeloma—even for relapsed or refractory disease.

Following is a summary of promising and recently approved therapies for blood cancers through 2024–2025:

CAR-T therapy for blood cancer

• What it is: A form of immunotherapy in which a patient's T cells are engineered to recognize and destroy cancer cells.

Used in:

• B-cell Acute Lymphoblastic Leukemia (ALL)
• Diffuse Large B-cell Lymphoma (DLBCL)
• Follicular Lymphoma
• Mantle Cell Lymphoma
• Multiple Myeloma (BCMA-targeted CAR-T)

Recent CAR-T treatments:

• Tisagenlecleucel (Kymriah)
• Axicabtagene ciloleucel (Yescarta)
• Idecabtagene vicleucel (Abecma) – multiple myeloma
• Ciltacabtagene autoleucel (Carvykti) – multiple myeloma

Targeted Therapy

Targeting blood cancer growth drivers through mutations or proteins:

• FLT3
• IDH1/2
• BTK
• BCL2
• EZH2
• PI3K
• JAK2

Bispecific Antibodies

• How they work: Bind to cancer cells and immune cells (e.g., T cells), uniting them for cancer destruction.

Examples:

• Blinatumomab (CD19/CD3) – B-cell ALL
• Mosunetuzumab (CD20/CD3) – relapsed follicular lymphoma
• Epcoritamab – large B-cell lymphoma
• Teclistamab (BCMA/CD3) – multiple myeloma

Antibody-Drug Conjugates (ADCs)

• Delivering chemotherapy using antibodies to target specific cells.

Examples:

• Brentuximab vedotin (anti-CD30) – Hodgkin lymphoma
• Inotuzumab ozogamicin (anti-CD22) – B-cell ALL
• Belantamab mafodotin – multiple myeloma (targeting BCMA)

Checkpoint Inhibitors

• Drugs releasing T cells by blocking "off switches" on immune cells.
• Particularly utilized in Hodgkin lymphoma.

Examples:

• Nivolumab
• Pembrolizumab
• Epigenetic Therapy
• Targets genes switched on/off by chemical tags.
• Drugs: Azacitidine, Decitabine (for AML/MDS), sometimes with Venetoclax.

Stem cell transplant for relapsed cancer

• Advances in haploidentical (half-matched) donor transplants
• Improved conditioning regimens and prevention of graft-vs-host disease
• May be utilized after CAR-T failure or in high-risk relapses

Clinical Trials and Personalized Medicine

New drugs are being tested in trials:

• Dual CAR-T cells (against greater than one antigen)
• NK cell therapy
• Small molecules inhibiting new targets (e.g., menin inhibitors in KMT2A/MLL-rearranged AML)
• Molecular profiling is now routine across many cancers to inform individualized treatments.

Chemotherapy for refractory cancer

Chemotherapy in refractory cancer is defined as the application of secondary or augmented chemotherapy approaches when conventional first-line treatment procedures are not successful. The tumor either remains unshrunk or keeps progressing despite initial treatment in refractory cancer. Such instances are usually more difficult and necessitate varied methods to attempt to gain control or remission.

Major Concepts of Chemotherapy for Refractory Cancer

Salvage Chemotherapy

• A term applied to chemotherapy administered after failure of conventional therapy.
• Usually involves new drug combinations or increased intensity regimens.
• Widespread in leukemias, lymphomas, and some solid cancers.

Examples by Cancer Type

• Acute Myeloid Leukemia (AML)
• Salvage regimens: FLAG-IDA, MEC, CLAG-M
• Targeted additions: Venetoclax + Decitabine or Azacitidine
• May bridge to stem cell transplant

Acute Lymphoblastic Leukemia (ALL)

• Regimens: Hyper-CVAD, FLAG, or nelarabine (for T-ALL)
• May combine with immunotherapies such as Blinatumomab or Inotuzumab

Diffuse Large B-cell Lymphoma (DLBCL)

• Salvage regimens: R-ICE, R-DHAP, R-GDP
• Followed by autologous stem cell transplant if responsive
• CAR-T cell therapy is considered when 2+ lines have failed

Multiple Myeloma

• Following failure of lenalidomide or bortezomib, regimens could include:
• Pomalidomide, Carfilzomib, Daratumumab
• Often used in combination: e.g., Daratumumab + dexamethasone + pomalidomide

Solid Tumors (e.g., Ovarian, Lung, Colon)

Refractory cases can utilize:

• Platinum-refractory ovarian cancer: Topotecan, PLD
• NSCLC: Docetaxel, gemcitabine, or trials with checkpoint inhibitors
• Colorectal: Irinotecan or regorafenib

Dose-Adjusted or High-Dose Chemotherapy

In certain hematologic cancers, dose escalation of chemotherapy can be utilized as a bridge to:

• Stem cell transplant (AML, ALL, lymphoma)
• Consolidation prior to CAR-T therapy

Addition to Targeted or Immune Therapy

Chemotherapy is increasingly added to:

• Targeted therapies (e.g., Venetoclax in AML, BTK inhibitors in CLL)
• Monoclonal antibodies (e.g., Rituximab in lymphomas)
• Checkpoint inhibitors (in selected solid tumors and Hodgkin lymphoma)

Blood cancer treatment in India

Treatment of blood cancer in India has come a long way, with numerous world-class hospitals providing cutting-edge treatments including chemotherapy, bone marrow transplant, immunotherapy, CAR-T cell therapy, and targeted therapies at international quality with relatively lower prices.

Relapsed acute lymphoblastic leukemia

Relapsed Acute Lymphoblastic Leukemia (ALL) is a grave condition where the leukemia relapses after remission. It affects children as well as adults, and the treatment varies according to age, genetic subtype, earlier treatment, and time to relapse.

Types of Relapse in ALL

• Early relapse: In 6–12 months of remission – usually more aggressive
• Late relapse: More than 12–24 months – could be better prognosis
• Isolated CNS or testicular relapse: Leukemia comes back only within the brain or testes
• Combined relapse: Leukemia recurs in bone marrow and other locations

Why Choose GetWellGo for Relapsed and Refractory Blood Cancer Treatment?

GetWellGo is regarded as a leading supplier of healthcare services. We help our foreign clients choose the best treatment locations that suit their needs both financially and medically.

We offer:

• Complete transparency
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• Expert oncologist with a strong track record of success
• Assistance during and after the course of treatment.
• Language Support
• Travel and Accommodation Services
• Case manager assigned to every patient to provide seamless support in and out of the hospital like appointment booking
• Local SIM Cards
• Currency Exchange
• Arranging Patient’s local food
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